Effect of Chemoradiotherapy with Gemcitabine and Cisplatin on Locoregional Control in Patients with Primary Inoperable Pancreatic Cancer

Gemcitabine sensitizes tumor cells to radiation and cisplatin and thereby enhances the cytotoxic effect of gemcitabine. Here we report the efficacy and toxicity of concurrent chemoradiation with gemcitabine and cisplatin in the treatment of patients with locally advanced, unresectable pancreatic cancer. A total of 47 patients (29 men, 18 women; median age 61 years) with histologically proven advanced pancreatic carcinoma were included in the study. They underwent chemotherapy with gemcitabine 300 mg/m² and cisplatin 30 mg/m² on days 1, 8, 22, and 29; concurrent radiation (45—50 Gy) was applied to the tumor and regional lymph nodes (1.8—2.0 Gy/fraction 5 days per week). Subsequent to chemoradiotherapy, treatment was continued with more two cycles of gemcitabine (1000 mg/m²) and cisplatin (50 mg/m²) applied on days 1 and 15 of a 4-week cycle. After completion of chemoradiotherapy, 9 patients (19.1%) achieved a complete response and 23 patients (48.9%) a partial response, for an overall response rate of 68%. The lesions were considered resectable in 27 patients, and 25 of the 27 patients underwent laparotomy. The other 20 patients underwent a definitive pancreatic resection. Altogether, 13 patients had negative surgical margins. With a median follow-up of 25.7 months (range 12.7—38.7 months) after completion of chemoradiation, distant metastasis had occurred in 23 patients and local recurrence in only 4 of 44 patients (8.5%). the median progression-free survival was 7.8 months (range 6.2—9.4 months). The median survival amounted to 10.7 months (range 8.4—13.0 months) for all patients, whereas it was prolonged to 24.2 months (range 6.8—41.7 months) for those undergoing R0 resection. The main toxicities associated with chemoradiation included grade 3/4 leukopenia (68% of patients) and thrombocytopenia (61%). Episodes of cholangitis were observed in 11 patients. We concluded that gemcitabine and cisplatin can safely be combined with external beam radiation. This preoperative treatment approach is highly effective and appears to improve survival in patients whose tumors are rendered completely resectable.     

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.     

Surgical resection following radiation therapy with concurrent gemcitabine in patients with previously unresectable adenocarcinoma of the pancreas

The combination of gemcitabine with concurrent radiation therapy (Gem/RT) is a promising new approach that is being investigated in patients with unresectable pancreatic cancer. However, substantial toxicity with this combination has also been observed. This review was conducted to determine whether Gem/RT could be safely delivered in the neoadjuvant setting, based on our experience with this combined therapy in a cohort of patients with previously unresectable pancreatic cancer, who subsequently underwent surgical resection. Between July 1996 and June 2001, a total of 67 patients with locally unresectable pancreatic cancer, without distant metastatic disease, received Gem/RT at our institution. Seventeen patients (25%) underwent exploratory surgery following Gem/RT, and nine underwent standard Whipple resection. Thus 9 (52%) of 17 patients who had exploratory operations or 9 (13%) of 67 patients, underwent surgical resection. Thirty-day mortality after resection was 0%, and there were no major surgical complications. Median length of hospital stay was 14 days (range 11 to 19 days). With a median follow-up of 32 months, median survival for the resected patients was 17.6 months (95% confidence interval 12.6 to 37.3 months). Median survival for the remaining 58 patients was 11.9 months (95% confidence interval 9.6 to 14.7 months, P = 0.013). We conclude that surgical resection may be safely performed after Gem/RT in a select group of patients initially considered to have unresectable pancreatic cancer. The use of Gem/RT in a neoadjuvant setting is currently being investigated in a multi-institutional phase II trial. Presented at the forty-fourth Annual Meeting of the American Society for Therapeutic Radiology and Oncology, New Orleans, Louisiana, October 6–10, 2002.     

Extended Neoadjuvant Chemotherapy for Borderline Resectable Pancreatic Cancer Demonstrates Promising Postoperative Outcomes and Survival

Background

The optimum approach to neoadjuvant therapy for patients with borderline resectable pancreatic cancer is undefined. Herein we report the outcomes of an extended neoadjuvant chemotherapy regimen in patients presenting with borderline resectable adenocarcinoma of the pancreatic head.

Methods

Patients identified as having borderline resectable pancreatic head cancer by American Hepato-Pancreato-Biliary Association/Society of Surgical Oncology consensus criteria from 2008 to 2012 were tracked in a prospectively maintained registry. Included patients were initiated on a 24-week course of neoadjuvant chemotherapy. Medically fit patients who completed neoadjuvant treatment without radiographic progression were offered resection with curative intent. Clinicopathologic variables and surgical outcomes were collected retrospectively and analyzed.

Results

Sixty-four patients with borderline resectable pancreatic cancer started neoadjuvant therapy. Thirty-nine (61 %) met resection criteria and underwent operative exploration with curative intent, and 31 (48 %) were resected. Of the resected patients, 18 (58 %) had positive lymph nodes, 15 (48 %) required en-bloc venous resection, 27 (87 %) had a R0 resection, and 3 (10 %) had a complete pathologic response. There were no postoperative deaths at 90 days, 16 % of patients had a severe complication, and the 30-day readmission rate was 10 %. The median overall survival of all 64 patients was 23.6 months, whereas that of unresectable patients was 15.4 months. Twenty-five of the resected patients (81 %) are still alive at a median follow-up of 21.6 months.

Conclusions

Extended neoadjuvant chemotherapy is well tolerated by patients with borderline resectable pancreatic head adenocarcinoma, selects a subset of patients for curative surgery with low perioperative morbidity, and is associated with favorable survival.     

Neoadjuvant Chemoradiotherapy for Adenocarcinoma of the Pancreas: Treatment Variables and Survival Duration

Background:For patients with potentially resectable pancreatic cancer, the poor outcome associated with resection alone and the survival advantage demonstrated for combined-modality therapy have stimulated interest in preoperative chemoradiotherapy. The goal of this study was to analyze the effects of different preoperative chemoradiotherapy schedules, intraoperative radiation therapy, patient factors, and histopathologic variables on survival duration and patterns of treatment failure in patients who underwent pancreaticoduodenectomy for adenocarcinoma of the pancreatic head.Methods:Data on 132 consecutive patients who received preoperative chemoradiation followed by pancreaticoduodenectomy for adenocarcinoma of the pancreatic head between June 1990 and June 1999 were retrieved from a prospective pancreatic tumor database. Patients received either 45.0 or 50.4 Gy radiation at 1.8 Gy per fraction in 28 fractions or 30.0 Gy at 3.0 Gy per fraction in 10 fractions with concomitant infusional chemotherapy (5-fluorouracil, paclitaxel, or gemcitabine). If restaging studies demonstrated no evidence of disease progression, patients underwent pancreaticoduodenectomy. All patients were evaluated with serial postoperative computed tomography scans to document first sites of tumor recurrence.Results:The overall median survival from the time of tissue diagnosis was 21 months (range 19–26, 95%CI). At last follow-up, 41 patients (31%) were alive with no clinical or radiographic evidence of disease. The survival duration was superior for women (P = .04) and for patients with no evidence of lymph node metastasis (P = .03). There was no difference in survival duration associated with patient age, dose of preoperative radiation therapy, the delivery of intraoperative radiotherapy, tumor grade, tumor size, retroperitoneal margin status, or the histologic grade of chemoradiation treatment effect.Conclusion:This analysis supports prior studies which suggest that the survival duration of patients with potentially resectable pancreatic cancer is maximized by the combination of chemoradiation and pancreaticoduodenectomy. Furthermore, there was no difference in survival duration between patients who received the less toxic rapid-fractionation chemoradiotherapy schedule (30 Gy, 2 weeks) and those who received standard-fractionation chemoradiotherapy (50.4 Gy, 5.5 weeks). Short-course rapid-fractionation preoperative chemoradiotherapy combined with pancreaticoduodenectomy, when performed on accurately staged patients, maximizes survival duration and is associated with a low incidence of local tumor recurrence.Presented at the 53rd Annual Cancer Symposium of the Society of Surgical Oncology, New Orleans, Louisiana, March 18, 2000     

Pancreatic Resections after Chemoradiotherapy for Locally Advanced Ductal Adenocarcinoma: Analysis of Perioperative Outcome and Survival

Background The most accepted treatment for locally advanced pancreatic cancer is chemoradiotherapy. However, indications to and results of pancreatic resections after chemoradiation are not yet defined.Methods From June 1999 to December 2003, 28 patients with locally advanced pancreatic cancer (group 1) were enrolled for institutional trials of gemcitabine-based chemoradiotherapy. Tumors were stratified as unresectable or borderline resectable according to the pattern of vascular involvement at pretreatment computed tomographic scan. Patients with partial response or stable disease and in-range Ca19-9 were surgically explored. Perioperative outcome and survival of group 1 were compared with 44 patients primary resected for localized cancer with or without adjuvant treatment in the same time period (group 2).Results Only one unresectable tumor was successfully resected compared to 7 out of 18 (39%) that were borderline resectable. Operations after chemoradiation were 1 hour longer and postoperative stays 5 days longer, but transfusion rate, morbidity, and mortality were not significantly different. Median survival was 15.4 months for group 1 (>21 for resected vs. 10 for not resected, P < 0.01) and 14 months for group 2. In both groups, a disease-free survival beyond 24 months was recorded only among patients resected with negative margins.Conclusions The conversion of an unresectable cancer to a resectable one is a rare event. On the contrary, the resection of a borderline resectable tumor was successfully accomplished in one-third of cases. Chemoradiotherapy did not increase the operative risk, but the interventions were more technically demanding and required a longer postoperative stay. Patients resected after chemoradiation for a locally advanced tumor had at least the same survival as those primary resected for a localized one. Only R0 resections in both groups gave the chance of disease-free survival longer than 24 months.     

Reoperative pancreaticoduodenectomy.

OBJECTIVE: The preoperative diagnostic strategy and operative technique for reoperative pancreaticoduodenectomy were outlined and operative mortality, perioperative morbidity, and early survival data in carefully selected patients undergoing reoperation for pancreatic cancer were analyzed. SUMMARY BACKGROUND DATA: Many patients with localized, nonmetastatic cancer of the pancreas undergo exploratory surgery with limited preoperative assessment of resectability. Frequently, pancreaticoduodenectomy is not performed because cytologic or histologic proof of diagnosis is lacking, or tumor resectability is questioned. Many patients are denied reoperation and a potentially curative resection because of the unacceptable morbidity and mortality believed to accompany pancreaticoduodenectomy in the reoperative setting. METHODS: Twenty-three patients who had undergone previous surgery for palliation or diagnosis of a pancreatic head mass were reoperated on after a standardized preoperative imaging evaluation consisting of chest radiography, computed tomography, and visceral angiography. A standardized operative technique was used on all patients, but was modified based on altered anatomy from the initial operation. RESULTS: Based on preoperative imaging studies, 19 of the 23 patients believed to have resectable tumors underwent laparotomy for planned pancreaticoduodenectomy; resection was accomplished in 14 patients. Seven of the fourteen patients required extended resections that included the superior mesenteric vein, right colon, or both. There was no perioperative mortality, and early complications occurred in 3 of the 14 resected patients. Four patients underwent planned palliative procedures. Four of ten patients who underwent resection for adenocarcinoma are without evidence of disease at a median follow-up of 26 months. CONCLUSIONS: Reoperative pancreaticoduodenectomy can be performed safely and may result in prolonged survival in carefully selected patients with resectable, localized pancreatic cancer.     

Preoperative chemoradiation for marginally resectable adenocarcinoma of the pancreas

Only 10% to 20% of patients with pancreatic cancer are considered candidates for curative resection at the time of diagnosis. We postulated that preoperative chemoradiation therapy might promote tumor regression, eradicate nodal metastases, and allow for definitive surgical resection in marginally resectable patients. The objective of this study was to evaluate the effect of a preoperative chemoradiation therapy regimen on tumor response, resectability, and local control among patients with marginally resectable adenocarcinoma of the pancreas and to report potential treatment-related toxicity. Patients with marginally resectable adenocarcinoma of the pancreas (defined as portal vein, superior mesenteric vein, or artery involvement) were eligible for this protocol. Patients received 50.4 to 56 Gy in 1.8 to 2.0 Gy/day fractions with concurrent protracted venous infusion of S-fluorouracil (250 mg/m²/day). Reevaluation for surgical resection occurred 4 to 6 weeks after therapy. Fifteen patients (9 men and 6 women) completed preoperative chemoradiation without interruption. One patient required a reduction in the dosage of S-fluorouracil because of stomatitis. Acute toxicity from chemoradiation consisted of grade 1 or 2 nausea, vomiting, diarrhea, stomatitis, palmar and plantar erythrodysesthesia, and hematologic suppression. CA 19-9 levels declined in all nine of the patients with elevated pretreatment levels. Nine of the 1.5 patients underwent a pancreaticoduodenectomy, and all had uninvolved surgical margins. Two of these patients had a complete pathologic response, and two had microscopic involvement of a single lymph node. With a median follow-up of 30 months, the median survival for resected patients was 30 months, whereas in the unresected group median survival was 8 months. Six of the nine patients who underwent resection remain alive and disease free with follow-up of 12, 30, 30, 34, 39, and 72 months, respectively. Preoperative chemoradiation therapy is well tolerated. It may downstage tumors, sterilize regional lymph nodes, and improve resectability in patients with marginally resectable pancreatic cancer. Greater patient accrual and longer follow-up are needed to more accurately assess its future role in therapy. Presented at the Eighty-Second Annual Meeting of the American Radium Society, London, England, April l–5, 2000.     

Peritoneal cytology in patients with potentially resectable adenocarcinoma of the pancreas

The prognostic significance of malignant cells in the peritoneal washings of patients with pancreatic adenocarcinoma remains poorly defined. Prior reports suggest that positive peritoneal cytology (PPC) is associated with advanced disease and reduced survival. To determine the prognostic value of PPC in patients with pancreatic cancer, we retrospectively reviewed our database between July 1987 and September 2002 and identified 168 patients who had undergone exploration for potentially resectable pancreatic cancer with peritoneal washings performed at the time of exploration. One hundred thirty-five patients underwent resection; 33 were considered unresectable. PPC was reported for 27 patients (16.1%): 13 (9.6%) in the resected and 14 (42.4%) in the unresected group. Median time to macroscopically detected recurrence in the resected group was not significantly different in the PPC versus negative peritoneal cytology (NPC) patients (10 vs 12 months, P = 0.46). Median overall survival of patients with PPC versus NPC approached, but did not reach, significance (15 vs 19 months, P = 0.055). Peritoneal cytology status was not associated with administration of chemoradiation, margin status, antecedent fine-needle aspiration, stage, or site of recurrence. These data suggest that malignant cells in peritoneal washings of patients with potentially resectable pancreatic adenocarcinoma should not preclude resection. Long-term survival may be achieved, therefore aggressive treatment should strongly be considered.     

Outcomes after resection of locally advanced or borderline resectable pancreatic cancer after neoadjuvant therapy

BackgroundNeoadjuvant treatment frequently is performed in unresectable/borderline resectable pancreatic cancer. The aim of this study was to retrospectively compare postoperative outcomes and survival of patients who underwent pancreatectomy after neoadjuvant treatment for locally advanced/borderline resectable pancreatic cancer (neoadjuvant treatment group) with those of patients with resectable disease who underwent upfront surgery.MethodsBetween 2000 and 2008, there were 403 patients who underwent pancreatic cancer resection, 41 (10.1%) patients after neoadjuvant treatment for initially unresectable tumors and 362 (89.9%) patients had upfront surgery. Univariate and multivariable analyses were performed.ResultsMortality/morbidity rates were similar in the 2 groups. Nodal metastases were significantly lower in the neoadjuvant treatment group (31.7% vs 86.2%; P < .001). A complete pathologic response was observed in 13.6% after neoadjuvant treatment. Median disease-specific survival from resection was 35 and 27 months in the neoadjuvant treatment and upfront groups, respectively (P = .74). In the neoadjuvant treatment group survival rates were similar in N0/N1 patients.ConclusionsPostoperative mortality and morbidity do not significantly increase after neoadjuvant treatment. Neoadjuvant treatment in locally advanced pancreatic cancer can lead to an objective pathologic response, but this does not significantly improve survival after resection.     

Microscopically incomplete resection offers acceptable palliation in pancreatic cancer

BACKGROUND: Because mortality and morbidity of pancreatic surgery have decreased to acceptable levels, the complex question arises whether pancreatic resection should be performed in patients with preoperatively doubtful resectable pancreatic cancer. METHODS: Perioperative parameters and outcome of 80 patients who underwent a microscopically incomplete (R1) resection were compared with those of 90 patients who underwent a bypass for locally advanced disease for pancreatic adenocarcinoma. All patients initially underwent exploratory laparotomy with the intention to perform a resection. Quality of life was assessed by analyzing readmissions and their indications. RESULTS: Groups were similar with respect to age, presenting symptoms, and preoperative health status. Tumors were significantly larger in the bypass group (3.5 cm vs 2.9 cm, P < .01). Hospital mortality was comparable: zero after R1 resection and 2% after bypass. Of all severe complications, only intra-abdominal hemorrhage occurred significantly more frequently after resection (10% vs 2%; P = .03). Hospital stay after resection was significantly longer than after bypass (16 vs 10 days; P < .01). Survival was significantly longer after R1 resection (15.8 vs 9.5 months, P < .01). Sixty-one percent of patients were readmitted for a total of 215 admissions, equally distributed between groups. After R1 resection, 0.58% of the total survival time after initial discharge was spent in the hospital, after bypass, 0.69%, which was not significantly different. CONCLUSIONS: R1 pancreatic resection and bypass for locally advanced disease can be performed with comparable low mortality and morbidity rates. Readmission rates are also comparable between groups and time spent in the hospital after initial discharge is low. Because resection offers adequate palliation in pancreatic cancer, a more aggressive surgical approach in patients who are found to have a doubtfully resectable tumor could be advocated, even if only an R1 resection can be achieved.     

Feasibility of pancreatectomy following high-dose proton therapy for unresectable pancreatic cancer

AIM To review surgical outcomes for patients undergoing pancreatectomy after proton therapy with concomitant capecitabine for initially unresectable pancreatic adenocarcinoma.METHODS From April 2010 to September 2013,15 patients with initially unresectable pancreatic cancer were treated withproton therapy with concomitant capecitabine at 1000 mg orally twice daily. All patients received 59.40 Gy(RBE) to the gross disease and 1 patient received 50.40 Gy(RBE) to high-risk nodal targets. There were no treatment interruptions and no chemotherapy dose reductions. Six patients achieved a radiographic response sufficient to justify surgical exploration,of whom 1 was identified as having intraperitoneal dissemination at the time of surgery and the planned pancreatectomy was aborted. Five patients underwent resection. Procedures included:Laparoscopic standard pancreaticoduodenectomy(n = 3),open pyloris-sparing pancreaticoduodenectomy(n = 1),and open distal pancreatectomy with irreversible electroporation(IRE) of a pancreatic head mass(n = 1). RESULTS The median patient age was 60 years(range,51-67). The median duration of surgery was 419 min(range,290-484),with a median estimated blood loss of 850 cm~3(range,300-2000),median ICU stay of 1 d(range,0-2),and median hospital stay of 10 d(range,5-14). Three patients were re-admitted to a hospital within 30 d after discharge for wound infection(n = 1),delayed gastric emptying(n = 1),and ischemic gastritis(n = 1). Two patients underwent R0 resections and demonstrated minimal residual disease in the final pathology specimen. One patient,after negative pancreatic head biopsies,underwent IRE followed by distal pancreatectomy with no tumor seen in the specimen. Two patients underwent R2 resections. Only 1 patient demonstrated ultimate local progression at the primary site. Median survival for the 5 resected patients was 24 mo(range,10-30).CONCLUSION Pancreatic resection for patients with initially unresectable cancers is feasible after high-dose [59.4 Gy(RBE)] proton radiotherapy with a high rate of local control,acceptable surgical morbidity,and a median survival of 24 mo.     

A Pilot Study of Preoperative Chemoradiotherapy for Resectable Gastric Cancer

Background: The goals of this study were to assess the feasibility and toxicity of a regimen of preoperative chemoradiotherapy, surgery, and intraoperative radiotherapy in the treatment of patients with potentially resectable gastric cancer. A secondary objective was to assess pathologic response to chemoradiotherapy in the treated tumors.Methods: Twenty-four patients were entered in the protocol. Treatment regimen consisted of 45 Gy of external beam radiotherapy with concurrent 5-FU given as a continuous infusion at a dose of 300 mg/m². Patients were restaged 4–6 weeks after chemoradiotherapy and then underwent surgical resection and intraoperative radiotherapy to a dose of 10 Gy.Results: Twenty-three patients (96%) completed chemoradiotherapy in accordance with the study protocol. Nineteen (83%) of 23 patients who completed chemoradiotherapy underwent surgical resection with D2 lymphadenectomy. Four patients (17%) had progressive disease and were not resected. The morbidity and mortality rates were 32% and 5%, respectively. Of the resected patients, two (11%) had complete pathologic responses while 12 (63%) had pathologic evidence of significant treatment effect.Conclusions: Preoperative chemoradiotherapy for gastric cancer can be delivered safely and is well tolerated. The rate of surgical complications is consistent with that of other recently reported prospective trials of gastrectomy alone. Preoperative chemoradiotherapy resulted in significant pathologic responses in the majority of treated tumors, and complete pathologic responses were achieved in some patients.     

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.     

Differences in survival for patients with resectable versus unresectable metastases from pancreatic islet cell cancer

Well-differentiated islet cell tumors can be associated with aggressive biology, resulting in early metastases to the liver. This study was carried out to determine whether survival for patients with malignant islet cell tumors and synchronous liver metastases is affected by complete surgical resection. Thirty-one patients with synchronous liver metastases from islet cell cancer underwent surgical exploration with the intent for complete tumor resection, and all patients underwent resection of the pancreatic primary. The patients were divided into two groups, those with resectable versus unresectable liver metastases. Twenty-six of 31 (84%) patients underwent complete resection of both the primary tumor and all liver metastases, and 5 (16%) patients underwent only complete resection of the pancreatic primary without liver resection. To extirpate the primary tumor, a pancreaticoduodenectomy was performed in 11 of the 26 (42%) completely resected patients and in 4 of the 5 (80%) incompletely resected patients, P = NS. The remainder of the patients underwent distal pancreatectomy. There were no statistical differences in primary tumor size, lymph node metastases, or adjuvant treatments between patients with resected and unresected liver metastases. The median overall survival for the completely resected group was 78 months, longer than the 17 months for the group with unresectable liver metastases (P = 0.06). Complete tumor resection (or the tumor biology that allows such complete resection) affords a survival advantage to patients with metastatic islet cell tumors of the pancreas. Patterns of liver metastases from islet cell tumors, specifically multiple bilobar metastases that are not amenable to resection and/or ablation, predict a poor outcome despite resection of the primary pancreatic tumor. Presented at the Thirty-Eighth Annual Meeting of The Pancreas Club, New Orleans, LA., May 16, 2004.     

Locally advanced non-small cell lung cancer completely resected after induction therapy

We analyzed 8 patients with unresectable locally advanced non-small cell lung cancer who responded to chemotherapy or chemoradiotherapy and underwent complete resection between June 2003 and June 2005. The patients were all male with a mean age of 61 years (range, 42 to 72 years). Histological subtypes included adenocarcinoma in 4 patients and squamous cell carcinoma in 4 patients. Clinical staging included T2N2M0 in 3 patients, T2N3M0 in 2 patients, and 1 patient each for T3N2M0, T4N2M0, and T4N3M0. Preoperative treatment included chemotherapy in 5 patients and chemoradiotherapy in 3 patients, all of whom had a partial response. Surgical procedures included lobectomy in 6 patients and pneumonectomy in 2 patients. In addition, all of the patients underwent mediastinal lymph node dissection (ND2a). Pathological effect included Ef. 0 in 1 patient, Ef. 1 in 2 patients, Ef. 2 in 2 patients, Ef. 3 in 3 patients. The median survival time from initial treatment (or surgery) was 16 (14) months in all cases, 22 (19) for ycN0, 12 (8) for ycN2, 31 (27) for Ef. 3, 13 (9) for Ef. 0-2, 27 (23) for pN0, 13 (9) for pN1-3, 31 (27) for chemoradiotherapy, 16 (13) for chemotherapy, 24 (21) for adenocarcinoma, and 15 (11) for squamous cell carcinoma. Multimodality treatment, including surgery, is beneficial for patients with unresectable locally advanced non-small cell lung cancer who respond to chemotherapy or chemoradiotherapy, especially those patients with ycN0 or pN0.     

胰腺癌外科治疗单中心10年临床经验分析

目的：探讨胰腺癌外科治疗的疗效。方法：回顾性分析我院普通外科2000--2010年经病理学检查或手术确诊的130例胰腺癌患者的临床资料。结果：130例胰腺癌患者中,首发症状前3位依次为腹痛、黄疸和消瘦,平均就诊时间91．99d。根治性切除27例（20．77％）,姑息性短路手术98例（75．38％）。I～II期患者手术切除率为85．19％,III～IV期为3．88％。根治性手术患者术后中位生存时间为20月,而捷径手术患者的术后中位生存时间为5月。结论：手术是目前治疗胰腺癌的唯一有效手段,I～II期患者手术切除率高,但预后并不令人满意。应加强胰腺癌的综合治疗,特别是对失去手术切除机会的中晚期患者的综合治疗。     

Multiple primary bronchogenic carcinomas: treatment and follow-up

A second primary bronchogenic carcinoma subsequently developed 8 to 156 months later in 19 patients who underwent curative resection of primary bronchogenic carcinomas. The second primary tumor was treated by surgical resection in 9 patients, 3 patients' tumors were considered unresectable, and the remaining 7 patients, despite having potentially resectable tumors, did not undergo resection because of insufficient pulmonary reserve or unwillingness to undergo resection. Actuarial life-table analysis of survival for the 9 patients who underwent resection showed a median survival time of 110.3 months compared with 19 months for the group with unresected but resectable tumors and 10.5 months for the group with unresectable tumors. There was no operative mortality in the group with resected tumors. We conclude that in patients in whom a second primary carcinoma of the lung develops, surgical resection prolongs survival and can be performed with a low operative mortality.     

Pancreatic carcinoma deemed unresectable at exploration may be resected for cure: an institutional experience

Only a minority of patients with a diagnosis of pancreatic adenocarcinoma (PA) have disease amenable to curative resection. Between April 1987 and March 1999, 40 patients with pancreatic adenocarcinoma deemed unresectable at exploration at other institutions were considered for neoadjuvant treatments and then re-evaluated for possible re-exploration. We retrospectively compared the clinical outcomes, including overall survival (OS), among three groups: Group A, 22 previously unresectable patients who were subsequently successfully resected, 20 after induction therapy; Group B, 31 patients who received preoperative chemoradiotherapy before their only operation; and Group C, 33 patients who were primarily resected, 27 of whom were then treated with adjuvant therapy. Of those resectable from Group A, 5 required portal venorrhaphy and 3 had hepatic artery reconstruction. Eighteen of the 40 patients were unresectable because of progression of disease with a mean OS of 8 months; 12 were assessed at second laparotomy; 6 were excluded from second operation on the basis of preoperative imaging studies. Kaplan-Meier curves showed no differences in OS among the three groups: OS in Group A was 34 months; Group B, 21; and Group C, 13 (P = 0.15). Margin status was comparable in all three groups (P = 0.52). As expected, nodal positivity was greatest in Group C (P = 0.001). There were no operative mortalities in Group A, and the morbidity rate was comparable with that of Groups B and C. Upon re-evaluation, many tumors (54%) previously deemed "unresectable" were surgically extirpated for cure with a median survival comparable with that of patients who did not undergo previous exploration.     

Utility of tumor markers in determining resectability of pancreatic cancer

HYPOTHESIS: Despite advances in preoperative radiologic imaging, a significant fraction of potentially resectable pancreatic cancers are found to be unresectable at laparotomy. We tested the hypothesis that preoperative serum levels of CA19-9 (cancer antigen) and carcinoembryonic antigen will identify patients with unresectable pancreatic cancer despite radiologic staging demonstrating resectable disease. DESIGN AND SETTING: Academic tertiary care referral center. PATIENTS: From March 1, 1996, to July 31, 2002, 125 patients were identified who underwent surgical exploration for potentially resectable pancreatic cancer based on a preoperative computed tomographic scan; in 89 of them a preoperative tumor marker had been measured. MAIN OUTCOME MEASURES: Preoperative tumor markers (CA19-9 and carcinoembryonic antigen) were correlated with extent of disease at exploration. As CA19-9 is excreted in the biliary system, CA19-9 adjusted for the degree of hyperbilirubinemia was determined and analyzed. RESULTS: Of the 89 patients, 40 (45%) had localized disease and underwent resection, 25 (28%) had locally advanced (unresectable) disease, and 24 (27%) had metastatic disease. The mean adjusted CA19-9 level was significantly lower in those with localized disease than those with locally advanced (63 vs 592; P =.003) or metastatic (63 vs 1387; P<.001) disease. When a threshold adjusted CA19-9 level of 150 was used, the positive predictive value for determination of unresectable disease was 88%. Carcinoembryonic antigen level was not correlated with extent of disease. CONCLUSIONS: Among the patients with resectable pancreatic cancer based on preoperative imaging studies, those with abnormally high serum levels of CA19-9 may have unresectable disease. These patients may benefit from additional staging modalities such as diagnostic laparoscopy to avoid unnecessary laparotomy.