Resective surgical treatment of exocrine pancreas neoplasms. Retrospective study of 294 cases and review of the literature

Authors report their own experience on the treatment of pancreatic neoplasms. Two-hundred-ninety-four patients were observed during the years 1959-95. Resectability rate was 18%. Fifty-three patients underwent pancreatic resection: 22 distal pancreatectomies (41.5%), 2 total pancreatectomies (3.7%) and 29 pancreaticoduodenectomies (54.7%) (7 PPPD). Overall morbidity rate was 15.6% with decrease during the years of major postoperative complications. More frequent complications were renal failure (4%), bleeding (1.7%) and acute pancreatitis (5.6%), which was absent during the 1981-95 period. Pancreatic fistula occurred in 5.6%, but in the years 1981-95 only one patient suffered from it (1.8%). During the years 1959-70 operative mortality rate after pancreatic resection was 22.7%, during 1971-80 was 12.5% and during 1981-95 decreased to 4.3%. Patients with stage I tumours survived curative pancreatic resection for about 18.2 months, compared with those with stage II and III tumours, who survived for about 15 and 13 months, respectively. Recent studies have demonstrated a reduction in the morbidity and mortality of pancreatic resections and improvement in the actuarial 5-year survival for patients with resected ductal adenocarcinoma. In the presence of lymphnode metastases, pancreaticoduodenectomy offers good palliation and meaningful survival. In the absence of lymphnode metastases, pancreaticoduodenectomy offers encouraging long-term survival rates and a chance for cure.     

Pylorus-preserving total pancreatectomy. Early and late results.

BACKGROUND/AIMS: Preservation of the pylorus is an accepted alternative procedure to the classical Whipple operation for pancreatic head resection but data describing its value for total pancreatectomy are sparse. METHODS: A prospective analysis of 22 total pancreatectomies performed in a consecutive series of 436 pancreatic resections from 1.11.93 to 1.5.99. RESULTS: 11 patients underwent total pancreatectomy with preservation of the pylorus. Histopathological examination revealed pancreatic adenocarcinoma in 16 cases and duodenal adenocarcinoma in 1 patient, 5 patients had other types of pancreatic neoplasm. In-hospital mortality was 4.5% (n = 1), cumulative morbidity was 59% and reoperations were performed in 9.1% of cases (n = 2). Median follow-up was 37 months (range 5-66). 62% of patients (n = 13) developed tumor recurrence and 13 patients died during the follow-up period with 10 deaths being cancer related. There was no difference concerning postoperative and follow-up morbidity of survival between patients undergoing pylorus-preserving total pancreatectomy or pancreatectomy with gastrectomy. However, postoperative body weight was increased 3, 6, 9 and 12 months following preservation of the pylorus. CONCLUSION: Total pancreatectomy with preservation of the pylorus is a feasible type of resection for all types of pancreatic or ampullary tumors, which shows a similar morbidity and long-term survival but improved nutritional recovery compared with standard total pancreatectomy.     

Survival After Pancreatectomy With Major Arterial Resection and Reconstruction

Background Absence of major arterial tumor involvement has generally been regarded as a major criterion for resectability of pancreatic tumors. We hypothesize that resection of a tumor-involved hepatic artery (HA) or celiac artery (CA) with reconstruction may offer a survival benefit to patients whose tumors were traditionally regarded as unresectable. Methods All patients with pancreatic adenocarcinoma treated between 1996 and 2007 were reviewed. Patients were included if they underwent resection of the HA or CA during pancreatectomy. Survival was analyzed by Kaplan-Meier survivor functions, Cox proportional hazard models, and the log rank test. Results Twelve patients (six men and six women) with adenocarcinoma underwent pancreatectomy with resection of a tumor-involved HA (n = 2) and/or CA (n = 10). Median age at diagnosis was 62 years (range, 53–73 years). All patients completed neoadjuvant chemoradiotherapy with or without full dose chemotherapy before resection. Procedures performed were six extended pancreaticoduodenectomies, two proximal subtotal pancreatectomies, two distal pancreatectomies, and two total pancreatectomies. Ten cases involved celiac resections, and two had isolated HA resections. The 60-day mortality was 17% (2 of 12). Median survival after diagnosis was 20 months (range, 6–41 months). Median survival after resection was 17 months (range, 1–36 months). Survival was not statistically significantly related to age, sex, margin status, or preoperative CA19-9 level. The 3-year survival was 17%. There were no 5-year survivors. Conclusions Resection of the HA or CA with reconstruction may prolong survival for selected patients who undergo pancreatic resection after neoadjuvant therapy. However, this aggressive approach did not result in any long-term survivors in our series.     

Long-term survival after resection for ductal adenocarcinoma of the pancreas. Is it really improving?

OBJECTIVE: The authors review their recent experience with resected pancreatic ductal adenocarcinoma. SUMMARY BACKGROUND DATA: Ductal adenocarcinoma of the pancreas has traditionally had a 5-year survival rate less than 10% after curative resection. Recently, several groups have reported markedly improved 5-year survival rates (approaching 25%) for patients undergoing curative resection. METHODS: Institutional experience with 186 consecutive patients (1981-1991) with pathologic diagnoses of ductal adenocarcinoma undergoing pancreatic resection was reviewed. Histologic specimens of all 3-year survivors (n = 31) were re-reviewed by two pathologists, one internal and one external; nonductal pancreatic cancers then were excluded. RESULTS: After histologic re-review, 12 patients did not have ductal adenocarcinoma, leaving a total of 174 patients for analysis (102 men, 72 women; mean age 63 years, range 34-82 years). Mean follow-up was 22 months (range 4-109). Classical pancreaticoduodenectomy was performed in 71%, pylorus-preserving resection in 9%, and total pancreatectomy in 20%. Hospital mortality was 3%. Twenty-eight patients (16%) had macroscopically incomplete resections; 98 (56%) had lymph node metastases within the resected specimens, and 21 patients (12%) had extensive perineural invasion. Overall actuarial 5-year survival was 6.8%. Five-year survival was greater for node-negative versus node-positive patients (14% vs. 1%, p < 0.001), and for smaller (< 2 cm) versus larger tumors (20% vs. 1%, p < 0.001). The 5-year survival for the subset of patients with negative nodes and no perineural or duodenal invasion (69 patients) was 23% (p < 0.001). Mean survival of the 12 excluded patients was 53 +/- 7 months compared with 17.5 +/- 1 months in the 174 patients with ductal pancreatic cancer. CONCLUSIONS: Five-year survival for patients undergoing pancreatic resection for lesions deemed to be clinically "curable" intraoperatively and histologically reviewed/confirmed to be ductal adenocarcinoma of the pancreas is approximately 7%. Survival is greater (23%) in the subset of patients with negative nodes and no duodenal or perineural invasions. Pathologic review of all patients with pancreatic ductal cancer adenocarcinoma is mandatory if survival data are to be meaningful.     

Factors influencing survival after resection for periampullary neoplasms

BACKGROUND: The purpose of this study was to determine predictors of survival after resection for periampullary neoplasms. METHODS: Over a 15-year period, 208 patients underwent laparotomy for periampullary neoplasms. Data were analyzed to assess predictors of survival. RESULTS: Pathologic examination showed pancreatic cancer (n = 136; 65%), ampullary cancer (n = 28; 13%), distal common bile duct cancer (n = 10; 5%), duodenal cancer (n = 4; 2%), neuroendocrine tumor (n = 11; 5%), cystadenocarcinoma (n = 4; 2%), cystadenoma (n = 5; 2%), and other (n = 10; 5%). A total of 129 patients underwent pancreatic resection (71 Whipples, 35 total pancreatectomies, 21 distal pancreatectomies, and 2 partial pancreatectomies) whereas 79 patients were found to be unresectable and underwent palliative bypass and/or biopsy. Median survival was 20.4 months for resectable patients versus 4.5 months for unresectable patients (P<0.001). Of the 129 resected patients, factors significantly (P<0.05) favoring long-term survival on univariate analysis included well-differentiated histology, common bile duct or ampullary adenocarcinoma, early stage, tumor diameter <2 cm, negative margins, and absence of lymph node metastases, perineural, or vascular invasion. Age, sex, race, and type of procedure had no influence on survival. On multivariate analysis, only tumor differentiation appeared independently related to survival. Using Kendall's tau analysis, tumor type and grade correlated significantly with all other predictors. CONCLUSIONS: Of all variables studied, tumor type and poor tumor differentiation in periampullary neoplasms appear to be markers that predict a constellation of other adverse findings.     

Significance of the depth of portal vein wall invasion after curative resection for pancreatic adenocarcinoma

HYPOTHESIS: The depth of portal vein (PV) wall invasion is a prognostic factor for survival after curative pancreatic resection for pancreatic ductal adenocarcinoma. DESIGN: Retrospective clinical study. SETTING: Department of digestive surgery and transplantation. PATIENTS: From January 1, 1990, through December 31, 2002, 121 patients underwent a curative pancreatic resection for ductal adenocarcinoma of the pancreas. Among these, 37 pancreatic resections combined with PV resection were performed. MAIN OUTCOME MEASURES: Prognostic factors for survival and predictive factors for the depth of PV wall invasion. RESULTS: The morbidity and mortality rates did not differ between patients undergoing or not undergoing PV resection (32.4% and 2.7% [1/37], respectively, vs 38.1% and 2.4% [2/84], respectively). The 3-year survival rate after curative pancreatic resection was significantly associated with the depth of PV wall invasion. Indeed, the 3-year overall survival rate was similar for patients with no PV invasion and those with superficial invasion into the tunica adventitia (40.0% vs 32.9%, respectively; P = .85). Deeper PV wall invasion into the tunica media or the tunica intima was associated with a poorer 1-year survival rate similar to that of patients undergoing noncurative resection (21.5% vs 34.4%, respectively; P = .53). Multivariate analysis showed that the depth of PV wall invasion, number of involved lymph nodes, and volume of blood transfusion were independent factors of overall and disease-free survival. Tumor size of 45 mm or more (evaluated by computed tomography) and angiographic type C or D on a portogram were significantly correlated with the depth of PV wall invasion. Patients presenting with both factors simultaneously had poor survival. CONCLUSIONS: The depth of PV wall invasion significantly alters survival after curative pancreatic resection combined with PV resection. However, occasional long-term survival could be observed after curative resection in patients with deep PV wall invasion.     

Recurrence patterns and postrecurrence survival after curative intent resection for pancreatic ductal adenocarcinoma

BackgroundPancreatic ductal adenocarcinoma has a high rate of recurrence after resection. We aimed to investigate patterns of recurrence of pancreatic ductal adenocarcinoma to identify opportunities for targeted intervention toward improving survival.MethodsThis was a retrospective analysis of consecutive patients that underwent curative-intent resection for pancreatic ductal adenocarcinoma between 2007 and 2015. Recurrence and survival were analyzed based on site of recurrence. Multiple clinicopathologic factors were calculated for likelihood of site-specific recurrence.ResultsThe study included 221 patients with median follow-up of 83 months. Median overall and recurrence-free survival was 19 and 13 months, respectively. Recurrence was observed in 71.9% patients. Local recurrence occurred in 16.4%, distant recurrence in 67.3%, and combined in 15.9%. The most common site of distant recurrence was the liver (49.7%) followed by lung (31.8%) and peritoneum (16.6%). Median time to liver recurrence was shortest (5 months, 95% confidence interval 1.7–8.3) and post recurrence survival was poor (4 months, 95% confidence interval 1.9–6.1). Patients with poorly differentiated tumors on pathology were 4.8 times more likely to recur in the liver (odds ratio 4.83, 95% confidence interval 1.7–13.9).ConclusionLiver metastasis after resection of pancreatic ductal adenocarcinoma occurs most frequently, earliest after surgery, and is rapidly fatal. Liver-directed therapies represent a target for future study.     

Reoperative surgery for periampullary adenocarcinoma.

In recent years, the morbidity, mortality, and long-term survival of patients undergoing surgery for periampullary adenocarcinoma have improved. These changes have prompted us to reoperate on patients who have previously undergone pancreatobiliary surgery, many of whom were initially considered to have unresectable lesions. From 1979 to 1990, 38 patients with pancreatic and 17 patients with nonpancreatic periampullary adenocarcinoma underwent reexploratory surgery at The Johns Hopkins Hospital, Baltimore, Md. Thirty-three (60%) of these 55 patients had resection at the time of second laparotomy. Of the 46 patients undergoing reexploratory surgery with an intent to resect, the overall resection rate was 72% (33), 64% (16/25) for pancreatic and 100% for nonpancreatic periampullary adenocarcinoma. Postoperative complications occurred in 21 patients (38%), but only one patient (2%) died following surgery. Mean survivals from reexploratory surgery were 6.9 months for the 22 patients with pancreatic cancer undergoing palliative surgery, 20.5 months for the 16 patients with resectable pancreatic cancer, and 33.0 months for the 17 patients with nonpancreatic periampullary adenocarcinoma undergoing resection. We conclude that in carefully selected patients, reoperative surgery for periampullary cancer (1) provides a significant resection rate, (2) can be performed safely, and (3) offers a chance for long-term survival.     

Isolated portal vein involvement in pancreatic adenocarcinoma. A contraindication for resection?

OBJECTIVE: This study was designed to examine the morbidity, mortality, and survival of patients undergoing portal vein resection (PVR) for adenocarcinoma of the pancreas. SUMMARY BACKGROUND DATA: Inability to separate the pancreas from the portal vein has historically been a locoregional contraindication for resection in patients with adenocarcinoma of the pancreas, and frequently, isolated local invasion of the portal veins is the only obstacle to curative resection. METHODS: A review of the prospective database for adenocarcinoma of the pancreas at Memorial Sloan-Kettering Cancer Center identified 332 patients who underwent pancreatic resection. Of those, 58 (17%) were identified as having isolated clinical involvement of the portal vein and underwent pancreatic resection with PVR. Patients undergoing curative pancreatic resection without PVR over this same time period comprise the control group. RESULTS: The 5% in-hospital mortality rate for PVR was not significantly different from that seen in those patients who did not undergo PVR (3%). Overall median survival for the PVR group was 13 months (range, < 1-109 months), which was not statistically different from those patients undergoing pancreatic resection without PVR (17 months (range, < 1-132 months). CONCLUSIONS: These results suggest that suspected isolated portal vein involvement should not be a contraindication for pancreatic resection in patients with adenocarcinoma.     

Preoperative chemoradiation in the management of adenocarcinoma of the body of the pancreas

Adenocarcinoma of the body of the pancreas has been traditionally associated with low resectability and poor prognosis. We reviewed 30 consecutive cases of pancreatic body adenocarcinoma presenting between 1988 and 2001. Twenty-six (87%) patients received preoperative chemotherapy (either 5-fluorouracil with or without mitomycin C or gemcitabine) plus radiation therapy (50.4 Gy), and four patients received chemoradiation postoperatively. During or shortly after chemoradiation 16 (53%) patients developed distant metastasis (n = 12), tumor progression (n = 2), or fatal septic complications (n = 2). Fourteen patients underwent surgical resection with curative intent. Resections performed included distal subtotal pancreatectomies (n = 6), extended pancreaticoduodenectomies (n = 6), and total pancreatectomies (n = 2). Ten patients (71%) required vascular reconstruction as a result of involvement of the portal vein or the superior mesenteric, hepatic arterial, or celiac vessels. Median overall survival was 34 months (range 8-152) for the resected group as compared with 8 months (range 1-14) in the unresected group (P = 0.005). Five-year actuarial overall survival is projected at 45 per cent for the resected group. In this poor-prognostic subset of patients with pancreatic cancer preoperative chemoradiation followed by an aggressive surgical approach was associated with resectability and long-term survival of a significant minority of patients.     

Carcinoma of the body and tail of the pancreas: is curative resection justified?

BACKGROUND. The role of resection in the treatment of carcinoma of the distal pancreas remains unclear. The less frequent occurrence of tumor in the distal gland, advanced tumor stage at diagnosis, and a lack of reported success have combined to produce therapeutic nihilism in the minds of many surgeons. The goal of this review was to assess long-term survival after distal pancreatectomy for carcinoma of the pancreas. METHODS. The records of all patients undergoing distal pancreatectomy at the Mayo Clinic for a primary pancreatic malignant tumor during the 25-year period from 1963 to 1987 were reviewed. Forty-four patients undergoing potentially curative distal pancreatectomies were identified: 26 patients for ductal adenocarcinoma, 12 patients for islet cell carcinoma, and six patients for cystadenocarcinoma. RESULTS. Major postoperative morbidity occurred in 9% of the patients and operative death in 2% of the patients. Patients with ductal adenocarcinoma frequently were admitted with advanced disease (stage II or III). The median overall survival for patients with ductal adenocarcinoma was 10 months. Fifteen percent of the patients survived 2 years after operation, and 8% of the patients survived 5 years. In contrast, the 5-year survival after resection of islet cell carcinomas and cystadenocarcinomas was excellent (83% and 100%, respectively). CONCLUSION. The prognosis for patients with ductal adenocarcinoma in the distal pancreas who were treated with potentially curative distal pancreatectomy is poor; however, the results are not substantially different from those reported after pancreaticoduodenectomy for malignant tumors of the proximal pancreas. Some patients with adenocarcinoma of the distal pancreas who were treated with resection may be long-term survivors. We recommend resection of carcinoma of the distal pancreas when the disease is limited to the gland and believe that all patients with ductal adenocarcinoma should be considered for postoperative adjuvant radiation and chemotherapy.     

Preoperative Platelet Count and Survival Prognosis in Resected Pancreatic Ductal Adenocarcinoma

BACKGROUND: High platelet counts are associated with an adverse effect on survival in various neoplastic entities. The prognostic relevance of preoperative platelet count in pancreatic cancer has not been clarified. METHODS: We performed a retrospective review of 205 patients with ductal adenocarcinoma who underwent surgical resection between 1990 and 2003. Demographic, surgical, and clinicopathologic variables were collected. A cutoff of 300,000/mul was used to define high platelet count. RESULTS: Of the 205 patients, 56 (27.4%) had a high platelet count, whereas 149 patients (72.6%) comprised the low platelet group. The overall median survival was 17 (2-178) months. The median survival of the high platelet group was 18 (2-137) months, and that of the low platelet group was 15 (2-178) months (p = 0.7). On multivariate analysis, lymph node metastasis, vascular invasion, positive margins, and CA 19-9 > 200 U/ml were all significantly associated with poor survival. CONCLUSIONS: There is no evidence to support preoperative platelet count as either an adverse or favorable prognostic factor in pancreatic ductal adenocarcinoma. Use of 5-year actual survival data confirms that lymph node metastases, positive margins, vascular invasion, and CA 19-9 are predictors of poor survival in resected pancreatic cancer.     

Pattern of lymph node involvement and prognosis in pancreatic adenocarcinoma: direct lymph node invasion has similar survival to node-negative disease

Lymph node status is one of the most important predictors of survival in pancreatic ductal adenocarcinoma. Surgically resected pancreatic adenocarcinoma is often locally invasive and may invade directly into peripancreatic lymph nodes. The significance of direct invasion into lymph nodes in the absence of true lymphatic metastases is unclear. The purpose of this study was to retrospectively compare clinical outcome in patients with pancreatic ductal adenocarcinoma with direct invasion into peripancreatic lymph nodes with patients with node-negative adenocarcinomas and patients with true lymphatic lymph node metastasis. A total of 380 patients with invasive pancreatic ductal adenocarcinoma classified as pT3, were evaluated: ductal adenocarcinoma with true lymphatic metastasis to regional lymph nodes (248 cases), ductal adenocarcinoma without lymph node involvement (97 cases), and ductal adenocarcinoma with regional lymph nodes involved only by direct invasion from the main tumor mass (35 cases). Isolated lymph node involvement by direct invasion occurred in 35 of 380 (9%) patients. Overall survival for patients with direct invasion of lymph nodes (median survival, 21 mo; 5-year overall survival, 36%) was not statistically different from patients with node-negative adenocarcinomas (median survival, 30 mo; 5-year overall survival, 31%) (P=0.609). Patients with node-negative adenocarcinomas had an improved survival compared with patients with lymph node involvement by true lymphatic metastasis (median survival, 15 mo; 5-year overall survival, 8%) (P<0.001) regardless of the number of lymph nodes involved by adenocarcinoma. There was a trend toward decreased overall survival for patients with 1 or 2 lymph nodes involved by true lymphatic metastasis compared with patients with direct invasion of tumor into lymph nodes (P=0.056). However, this did not reach statistical significance. Our results indicate that patients with isolated direct lymph node invasion have a comparable overall survival with patients with node-negative adenocarcinomas as opposed to true lymphatic lymph node metastasis.     

Clinical Implications of Combined Portal Vein Resection as a Palliative Procedure in Patients Undergoing Pancreaticoduodenectomy for Pancreatic Head Carcinoma

Background The clinical implications of combined portal vein resections are controversial.Methods One-hundred and forty-nine consecutive patients underwent macroscopically curative pancreatectomies for pancreatic head carcinoma between January 1, 1996 and December 31, 2004. Portal vein resection was performed in 86 patients (58%). Data on surgical mortality, morbidity, perioperative outcome, pathological factors, initial recurrence site, and survival were retrospectively compared between the patients with and without portal vein resection.Results The incidence of postoperative pancreatic fistula was lower among patients who underwent portal vein resection. The median survival period was 14 months for the portal vein resection group and 35 months for the non-portal vein resection group, respectively. Combined portal vein resection was a significant predictor of poor survival using a multivariate analysis. Portal vein resection was strongly associated with larger tumor size, the degree of retropancreatic tissue invasion, the presence of extrapancreatic nerve plexus invasion, lymph node metastases, and positive cancer infiltration at the surgical margins.Conclusions Portal vein resection at the time of pancreaticoduodenectomy can be safely performed. However, most of patients requiring portal vein resection do not achieve a potentially curative resection or a favorable survival term. As a result, the aggressive application and the strict selection of portal vein resection might reduce the incidence of positive surgical margins, enabling long-term survival in patients who do not require portal vein resection.     

Long-term outcomes following en bloc resection for pancreatic ductal adenocarcinoma of the head with portomesenteric venous invasion

BackgroundThe aim of this study is to clarify the prognostic influence of venous resection of the portal vein (PV) or superior mesenteric vein (SMV) on long-term outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) of the head with suspected vascular invasion.MethodsFrom May 1995 to December 2014, a total of 557 patients underwent surgery with curative intent for pancreatic cancer of the head.ResultsAmong 557 patients, 106 (19%) underwent pancreaticoduodenectomy (PD) with PV-SMV resection and 89 (75.5%) of these patients were confirmed to have true pathological invasion. The 5-year overall survival rate in patients underwent PV-SMV resection was significantly lower compared with those who did not (18.7% versus 24.3%; p = 0.002). Patients with negative resection margins who underwent PV-SMV resection had a better prognosis than those with positive resection margins who did not undergo PV-SMV resection with positive resection margins (17% versus 6.3% in 5-year overall survival rate; p = 0.003). The overall morbidity rate was not significantly different between PV-SMV resection group and no PV-SMV resection group (p = 0.064). On multivariate analysis, margin status, advanced T stage (3 or 4), lymph node metastasis, and adjuvant therapy were independent prognostic factors for survival.ConclusionPV-SMV resection was related to lower overall survival. However, on multivariate analysis, margin status was a more important prognostic factor than PV-SMV resection and true pathological invasion for survival. Therefore, en bloc PV-SMV resection should be performed when PV-SMV invasion is suspected to achieve R0 resection.     

Effect of curative versus palliative surgical treatment for stage III pancreatic cancer patients.

During the last decade, significant progress has been made in pancreaticoduodenectomy for patients with pancreatic carcinoma. Pancreatic resection performed by surgeons in tertiary referral centres is therefore justified, while the indications for pancreatic resection could be extended in patients with advance stages of disease. The aim of our study is to compare the effect of curative (pancreaticoduodenectomy) versus palliative surgery in patients with stage III pancreatic cancer, during a 20-years period. We retrospectively reviewed the charts of 58 consecutive patients with stage III ductal adenocarcinoma of the head of the pancreas. 23 patients underwent pancreatoduodenectomy with curative intent while the remaining 35 patients had surgery for palliative purposes (combined biliary and gastric bypass was performed in 83%). The hospital mortality rate was similar in both groups (4% vs 6%). 43% of patients undergoing pancreaticoduodenectomy had an uncomplicated post-operative course compared with 49% of patients undergoing palliative bypass. The length of surgical procedure and post-operative hospital stay in pancreaticoduodenectomy group were significant longer compared to those patients undergoing palliative bypass (p = 0.03 and p = 0.02 respectively). The overall actuarial survival was significantly (p < 0.01) longer in the group of patients who underwent pancreaticoduodenectomy compared with the group with palliative intent surgery. CONCLUSION: Pancreaticoduodenectomy with curative intent for stage III pancreatic cancer patients, could improve prognosis with similar peri-operative morbidity and mortality when compared with palliative bypass.     

Prognostic factors in the operative treatment of ductal pancreatic carcinoma

Background and aims: The average 5-year survival rate following resection of a ductal adenocarcinoma of the pancreas is 10%, worldwide. Despite increasing resection rates, only about 20% can be operated on with curative intent. A differential histopathological analysis of the resected tumors may help to justify expanding the surgical procedure by extended lymph-node dissection. Patients/methods: Between January 1986 and December 1995, a total of 113 patients underwent resection with curative intent for a ductal pancreatic carcinoma with regional lymph-node dissection. All histological findings were reviewed and reclassified in accordance with the 1997 Union Internationale Contra la Cancrum (UICC) classification. Survival data for all of these patients were obtained from family doctors and registration offices. Independent prognostic factors were statistically analyzed. Results: Of the 113 patients, 93 received an R0 resection. The postoperative mortality rate was 2.2% (2 of 93). More than one-half of the tumors had a diameter of between 2.1 cm and 4 cm. Among the 22 tumors measuring up to 2 cm in diameter, 41% already had lymph-node metastasis and 86% invasion of the lymphatic vessels. Carcinomas measuring between 4.1 cm and 6 cm were all associated with lymph-vessel invasion. Perineural invasion was present in 50% of the tumors. A noteworthy finding was the fact that 64% of the 25 tumors with negative lymph nodes had lymph-vessel invasion, and 48% perineural invasion. The cumulative 5-year survival rate of the R0-resected patients was 10.5%. Patients with lymph-node-negative stages survived significantly longer (26.5%) than patients with lymph-node-positive stages (5%). Furthermore, a significant difference was seen between pN1a and pN1b (16.7% vs 2.2%). Multivariate analysis identified tumor grading, tumor size and lymph vessel invasion as independent prognostic factors. Conclusions: Apart from the factors tumor size and tumor grading, lymph-vessel invasion appears to be of special significance for the long-term prognosis. Already in the pN0 stage, the latter was present in 64% of the cases and must be considered a precursor of lymphogenic metastasization. Since lymph-vessel invasion was demonstrated in 86% of tumors measuring less than 2 cm, the therapeutic consequence for all ductal pancreatic tumors is an extended lymphatic and soft tissue dissection that goes beyond the regional lymph-node stations. Received: 5 May 1999; in revised form: 30 July 1999 Accepted: 20 August 1999     

Surgery for recurrent pancreatic ductal adenocarcinoma

OBJECTIVE: This study evaluates the outcome of patients who underwent surgery for recurrent pancreatic cancer. SUMMARY BACKGROUND DATA: Recurrence of pancreatic ductal adenocarcinoma occurs in up to 80% of pancreatic cancer patients within 2 years of a potential curative resection because, in most cases, occult (local and/or distant) micrometastases are present at the time of the initial resection. METHODS: Thirty patients were operated for recurrent pancreatic cancer between October 2001 and April 2005. Median time between the initial resection and recurrence was 12.0 months. While 15 patients were resected, 15 patients either underwent palliative bypass or only exploration. Prospectively recorded data were analyzed retrospectively. Survival analysis was performed using Kaplan-Meier estimation and log-rank test. RESULTS: The overall median survival of patients with recurrent disease was 29.0 months. After the first reresection/exploration for recurrent disease, the median survival was 11.4 months. There was a tendency of increased median survival in the group of patients undergoing resection (17.0 months) compared with the bypass/exploration group (9.4 months), although this difference was not significant (P = 0.084). In addition, patients with a prolonged interval (>9 months) from resection to recurrence were more likely to benefit from reresection compared with patients with recurrence within 9 months (median survival 17.0 vs. 7.4 months; P = 0.004). The in-hospital morbidity and mortality rate of resected patients was 20% and 6.7% compared with 13.3% and 0% of patients who underwent only exploration/palliative bypass. CONCLUSION: Resection for recurrent pancreatic cancer can be carried out safely. Further studies are required to address the question whether a subgroup of patients might actually benefit from this procedure.     

环状RNA-PCAC1促进胰腺导管腺癌侵袭转移的研究

目的探讨环状RNA（circRNA）-PCAC1在胰腺导管腺癌中的表达水平及其与患者临床病理特征、预后的关系。 方法鉴定circRNA-PCAC1，并通过功能实验观察其对胰腺导管腺癌侵袭转移能力的影响。采用RT-PCR检测76例胰腺导管腺癌组织与配对癌旁组织的circRNA-PCAC1表达水平，Cox回归模型和Kaplan-Meier曲线法分析circRNA-PCAC1与患者临床病理特征和预后的关系。 结果功能实验证实circRNA-PCAC1过表达显著促进胰腺导管腺癌侵袭转移能力。胰腺导管腺癌组织中circRNA-PCAC1的表达水平显著高于癌旁组织（P<0.01）。circRNA-PCAC1过表达与胰腺导管腺癌患者不良预后相关（P<0.05）。circRNA-PCAC1是胰腺导管腺癌患者总生存期（HR=1.733，95% CI：1.066~2.991，P=0.030）和无病生存期（HR=1.636，95% CI：1.090~2.811，P=0.042）的独立影响因素。 结论circRNA-PCAC1在胰腺导管腺癌中高表达并促进胰腺导管腺癌侵袭转移，提示其可能成为胰腺导管腺癌临床治疗的新靶点。     

En bloc vascular resection for locally advanced pancreatic malignancies infiltrating major blood vessels: perioperative outcome and long-term survival in 136 patients

BACKGROUND: To assess in-hospital complication rates and survival duration after en bloc vascular resection (VR) for infiltration of pancreatic malignancies in major vessels. METHODS: Between 1994 and 2005, 585 patients underwent potentially curative pancreatic resection without adjuvant chemotherapy. Four hundred forty-nine patients (77%) underwent standard oncologic resection (VR-), whereas 136 (23%) received VR (VR+). For calculation of in-hospital morbidity and mortality rates, all 136 patients who underwent VR were considered. In contrast, for survival analysis, only pancreatic adenocarcinoma patients (n = 100) were included. RESULTS: One hundred twenty-eight VR+ patients underwent portal or superior mesenteric vein resection and 13 hepatic artery (HA) or superior mesenteric artery (SMA) resection. In 5 patients, synchronous VR addressing both the mesenterico-portal axis and either the HA or SMA was performed. In-hospital morbidity and mortality rates of VR- patients (39.7%/4.0%) nearly equaled that of VR+ patients (40.3%/3.7%). From the 100 patients with pancreatic adenocarcinoma, histopathology confirmed "true" vascular invasion in 77 patients. Twenty-three patients had peritumoral inflammation, mimicking tumor invasion. Median survival was 15 months (11.2-18.8) in patients with histopathologic proven vascular invasion and 16 months (14.0-17.9) in those without (P = 0.86). Two-year survival probabilities were 36% (without) versus 34% (with vascular invasion; P = 0.9). Among VR+ patients with histopathologically evidenced vascular invasion, 19 survived longer than 30 months, and 6 were still alive 5 years after surgery. Multivariate modeling identified nodal involvement (N1) and poor grading (G3) as the only predictors of decreased survival. Evidence of vascular invasion had no adverse impact on survival. CONCLUSION: Postoperative morbidity and mortality rates after en bloc VR are comparable with "standard" pancreatectomy procedures. Median survival of 15 months in patients with vascular invasion is superior to that of patients who undergo palliative therapy and nearly equals that of patients who are not in need for VR.