The Role of Extended Lymphadenectomy for Adenocarcinoma of the Head of the Pancreas: Strength of the Evidence

With improvements in the safety of Whipple resection in recent decades, surgeons have continued to explore the role of more extensive lymphadenectomy in hope of improving long-term survival. A systematic literature search of level I evidence addressing the role of the extent of lymphadenectomy was undertaken. Only reports of prospective, randomized controlled trials comparing pancreaticoduodenectomy with standard lymphadenectomy to pancreaticoduodenectomy with extended lymphadenectomy where information regarding survival, morbidity, mortality, the number of resected lymph nodes in each group and detailed operative technique were included. Four prospective, randomized trials comprising some 424 patients and one meta-analysis were identified. In aggregate, these studies confirmed that the number of resected lymph nodes was significantly higher in the pancreaticoduodenectomy with extended lymphadenectomy group. Morbidity and mortality rates were comparable. Postoperative diarrhea in the early months after operation was problematic in patients undergoing extended lymphadenectomy. In none of the studies was a benefit in long-term survival demonstrated. Standard pancreaticoduodenectomy continues to be the operation of choice for adenocarcinoma of the head of the pancreas. Presented at The Society for Surgery of the Alimentary Tract Postgraduate Course “Systematic Reviews of Pancreaticobiliary Disease Customized for the Gastroenterologist and Gastrointestinal Surgeon” on May 20, 2007, Washington, D.C.     

Meta-analysis of the Efficacies of Extended and Standard Pancreatoduodenectomy for Ductal Adenocarcinoma of the Head of the Pancreas

Background

The purpose of the present study was to evaluate the efficacy of extended pancreatoduodenectomy (EPD) and standard pancreatoduodenectomy (SPD) for ductal adenocarcinoma of the head of the pancreas via meta-analysis.

Methods

Relevant articles (published between 1995 and 2012) were compiled from online data sources. A total of nine studies satisfied the selection criteria, including a total of 973 patients (478 in the SPD group and 495 in the EPD group). Evaluation parameters included 1-, 3-, and 5-year survival, as well as mortality, morbidity, and specific morbidity outcomes.

Results

Meta-analysis revealed (1) differences in morbidity (Odds ratio [OR] = 1.740; 95 % confidence interval [CI], 0.840–3.600; P = 0.140), mortality (OR = 0.890; 95 % CI, 0.560–1.400; P = 0.620), 1-year overall survival (OS) rate (OR = 1.20; 95 % CI, 0.490–2.930; P = 0.69), 3-year OS rate (OR = 0.770; 95 % CI, 0.460–1.280; P = 0.190), and 5-year OS rate (OR = 1.12; 95 % CI, 0.690–1.810; P = 0.560) were not significant between EPD and SPD. (2) For bile leak (OR = 2.640; 95 % CI, 1.040–6.700; P = 0.040), pancreatic leak (OR = 1.740; 95 % CI, 1.040–2.91; P = 0.030), delayed gastric emptying (OR = 2.090; 95 % CI, 1.240–3.520; P = 0.006), and lymphatic fistula (OR = 6.120; 95 % CI, 1.06–35.320; P = 0.040) differences between EPD and SPD were significant, whereas other specific morbidities were not significantly different.

Conclusions

Extended pancreatoduodenectomy does not improve 1-, 3-, 5-year OS rates compared to SPD and there is a trend toward increased bile leak, pancreatic leak, delayed gastric emptying, and lymphatic fistula after EPD.     

Neoadjuvant Chemoradiation for Localized Adenocarcinoma of the Pancreas

Background: The use of neoadjuvant preoperative chemoradiotherapy CRT for pancreatic cancer has been advocated for its potential ability to optimize patient selection for surgical resection and to downstage locally advanced tumors. This article reports our experience with neoadjuvant CRT for localized pancreatic cancer.Methods: Since 1995, 111 patients with radiographically localized, pathologically confirmed pancreatic adenocarcinoma have received neoadjuvant external beam radiation therapy EBRT; median, 4500 cGy with 5-flourouracil–based chemotherapy. Tumors were defined as potentially resectable PR, n = 53 in the absence of arterial involvement and venous occlusion and locally advanced LA, n = 58 with arterial involvement or venous occlusion by CT.Results: Five patients 4.5% were not restaged due to death n = 3 or intolerance of therapy n = 2. Twenty-one patients 19% manifested distant metastatic disease on restaging CT. Twenty-eight patients with initially PR tumors 53% and 11 patients with initially LA tumors 19% were resected after CRT. Histologic examination revealed significant fibrosis in all resected specimens and two complete responses. Surgical margins were negative in 72%, and lymph nodes were negative in 70% of resected patients. Median survival in resected patients has not been reached at a median follow-up of 16 months.Conclusions: Neoadjuvant CRT provided an opportunity for patients with occult metastatic disease to avoid the morbidity of resection and resulted in tumor downstaging in a minority of patients with LA tumors. Survival after neoadjuvant CRT and resection appears to be at least comparable to survival after resection and adjuvant postoperative CRT.Presented at the 54th Annual Meeting of the Society of Surgical Oncology, Washington, DC, March 15-18, 2001.     

Adjuvant Chemoradiation Therapy for Adenocarcinoma of the Distal Pancreas

Background

This study was designed to examine the effect of adjuvant 5-FU-based chemoradiation therapy (CRT) after distal pancreatectomy for adenocarcinoma of the distal pancreas.

Methods

All patients underwent curative resection for adenocarcinoma of the distal pancreas between December 1985 and June 2006. Patients who received adjuvant CRT were compared with those who underwent surgery alone. A Kaplan–Meier estimate of the survival curve was used to determine estimates of the median survival and proportion alive at 1 and 2 years; log-rank tests were used to make comparisons between groups.

Results

A total of 123 patients underwent distal pancreatectomy; 29 patients were excluded for distant metastases at the time of surgery (n = 12, 10%) or before adjuvant therapy (n = 11, 9%), death within 2 months of surgery (n = 2, 2%), or if CRT treatment status was unknown (n = 4, 3%). Of the remaining 94 patients, 72% received adjuvant 5-FU-based CRT and 28% underwent surgery alone. Overall median survival was 16.2 (95% confidence interval (CI), 13.1–18.9) months. The groups were similar with respect to tumor size, nodal status, and margin status. There was no significant difference in overall survival between patients treated with adjuvant CRT versus surgery alone (p = 0.23). An exploratory subgroup analysis suggested a potential survival benefit of adjuvant CRT in patients with lymph node metastases (16.7 vs. 12.1 months, p < 0.01).

Conclusions

Adjuvant CRT did not increase survival compared with surgery alone; however, patients with node-positive disease appear to benefit from adjuvant CRT.     

胰腺癌根治性手术的再认识和展望

目前，对于胰腺癌惟一有治愈可能的方法依然是手术治疗，胰十二指肠切除术仍然作为胰头癌外科治疗的主要手段。但手术治疗后的肿瘤复发率高和长期生存率低仍然是困扰外科医师的一个难题。由于胰腺癌有早期淋巴结转移的特点，即使直径小于2cm的肿瘤，也极易发生胰周淋巴结转移，转移率高达30％以上。并且一些研究证实，根治性手术后未发现有淋巴结转移的胰腺癌患者的5年生存率也只有25％左右，其余患者仍死于局部复发和远处转移。     

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     

胰头癌的外科治疗

目的:探讨胰头癌的外科治疗.方法:因术前临床诊断胰头癌施行胰十二指肠切除术265例,其中行常规胰十二指肠切除术(WhiPPle)152例,保留幽门型胰十二指肠切除术(PPPD)75例,包括切除一段血管的胰十二指肠切除术19例,经再次手术行胰十二指肠切除术17例,全胰切除术2例.术前经B超、CT、选择性ERCP、穿刺细胞学检查,确诊232例(87.5%).术后经病理证实:胰头癌132例,壶腹癌77例,胆总管远端癌22例,十二指肠癌16例,转移癌1例和良性病变17例(慢性胰腺炎14例和良性肿瘤3例).结果:术后发生并发症118例(47.6%),住院死亡10例(4%).PPPD术后并发胃排空障碍较其它术式显著增高(P<0.01).结论:由非胰腺专业组医师施行的手术死亡率明显高于专业组医师(P<0.05),只要病例选择恰当,围手术期良好的处理,可以继续降低手术死亡率.     

Impact of Selection Bias on the Utilization of Adjuvant Therapy for Pancreas Adenocarcinoma

Background  

Improved outcomes have been associated with the use of adjuvant therapy after resection of pancreas adenocarcinoma. However, the frequency with which patients receive adjuvant therapy and the factors impacting its use remain largely undefined. We hypothesized that nonutilization of adjuvant therapy was primarily associated with patient comorbidity and onset of postoperative complications.     

Adenosquamous Versus Adenocarcinoma of the Pancreas: A Population-Based Outcomes Analysis

Background  

Pancreatic adenosquamous carcinoma has historically been characterized as having a more aggressive clinical course than ductal adenocarcinoma. The natural history of this disease, however, is essentially unknown.     

Duodenum-Preserving Resection of the Head of the Pancreas: The Significance as a Diagnostic Therapy for the Lesion in the Pancreatic Head

A 75-year-old man who was diagnosed as having mucin-producing pancreatic cystic lesion ofthe main pancreatic duct by duodenoscopic examination was reported. Because of the low malignant potential of such lesions, duodenum-preserving resection of the head of the pancreas was performed, and the intra-operative histological examination showed no malig-nancy of the resected pancreatic head and no other surgical procedures, such as lymph-adenectomy nor pancreato-duodenectomy were necessary. The significance of this case report lies in that a less invasive operation should be selected at first to diagnose whether the lesion is malignant or not, and als0 that the selected operation itself must be sufficient to resect an adequate part of the pancreatic tissue involving the cystic lesion, ifnot malignant. Here, we report the process to select the procedure and the surgical technique.     

Preoperative Chemoradiation for Patients With Locally Advanced Adenocarcinoma of the Pancreas

Background: Improved resectability is a major theoretical benefit of preoperative chemoradiation for pancreatic cancer. Since 1994, patients at Duke University Medical Center with locally advanced pancreatic cancer have been treated with multimodality preoperative therapy. The purpose of this study was to review our experience with preoperative therapy for locally advanced pancreatic cancer and determine if an aggressive neoadjuvant regimen would not only downstage these tumors pathologically but also improve the odds of complete surgical resection.Methods: The charts of 25 patients treated with neoadjuvant chemoradiation at Duke University Medical Center with biopsy-proven, locally advanced adenocarcinoma of the pancreas were reviewed. Tumors were defined as locally advanced based on radiographic or intraoperative evidence of disease that abuts the superior mesenteric artery or vein (n = 22) or involves lymph nodes that are within the proposed radiation field (n = 3). All 25 patients received external beam radiotherapy (median dose 4500 cGy) in daily fractions of 180 cGy over 5 weeks. All patients concurrently received 5-fluorouracil (FU), and many also received mitomycin C or cisplatin, or both. Patients were given a 3- to 4-week break before a restaging computed tomographic (CT) scan was performed. Three patients were not restaged: one died from metastatic disease; one was reclassified as having a neuroendocrine tumor; and one was lost to follow-up.Results: On restaging after neoadjuvant therapy, 64% of patients had stable or decreased primary tumor size. Radiographically, two patients appeared potentially resectable, and seven others developed evidence of metastatic disease. Eight patients underwent exploration, but only five could be resected. Of the five patients resected, only one had negative margins and negative lymph nodes. This patient had significant pancreatitis on initial exploration. After neoadjuvant therapy, he had a complete response radiographically, and there was no residual cancer in his resection specimen. Pathologic examination of the other resection specimens suggested that despite significant tumor fibrosis, malignant cells persist even at the periphery of the lesions.Conclusion: Although neoadjuvant chemoradiation has many theoretical advantages in managing pancreatic malignancy, true pathologic downstaging of locally advanced lesions into tumors that can be removed with negative nodes and margins appears to be a rare event with currently used therapeutic regimens.     

Molecular Evaluation of Colorectal Adenocarcinoma: Current Practice and Emerging Concepts

Molecular testing in colorectal cancer helps to address multiple clinical needs. Evaluating the mismatch repair pathway status is the most common use for molecular diagnostics and this testing provides prognostic information, guides therapeutic decisions and helps identify Lynch syndrome patients. For patients with metastatic colorectal cancer, testing for activating mutations in downstream components of the EGFR signaling pathway can identify patients who will benefit from anti-EGFR therapy. Emerging molecular tests for colorectal cancer will help further refine patient selection for targeted therapies and may provide new options for monitoring disease recurrence and the development of treatment resistance.     

胰头癌行胰十二指肠切除术淋巴结清扫范围及手术技巧

胰腺癌是高度恶性的消化系统肿瘤,其全球死亡率居恶性肿瘤的第4位。目前,手术切除仍旧是胰腺癌患者获得长久生存并有望治愈的唯一治疗方式。尽管在过去的数十年里,胰腺癌的手术技术和方式得以逐步完善,根治性切除术可使胰腺癌患者的5年生存率达到15％～25％。     

Adjuvant Therapy for Adenocarcinoma of the Pancreas: Analysis of Reported Trials and Recommendations for Future Progress

The delivery of postoperative combined modality adjuvant therapy for completely resected pancreatic cancer was initially shown to be beneficial on the basis of a prospective, randomized trial published in 1985. Since then, oncologists have debated whether chemotherapy, chemoradiation, or both is optimal adjuvant therapy after pancreatectomy for ductal adenocarcinoma of the pancreas; no global consensus has emerged. Unfortunately, despite the completion of a number of subsequent randomized trials of adjuvant therapy since 1985, no further improvements in overall survival have materialized. This lack of progress is not simply the result of ineffective systemic therapies, but in part the result of poor trial design and calls for a more disciplined approach to the selection of patients for surgery, pathologic assessment of surgical resection margins, and postoperative (pretreatment) imaging. This is the only way to ensure that patients who receive adjuvant therapy are actually receiving therapy for radiographically occult possible microscopic disease, rather than therapy for incompletely resected locally advanced disease or early postoperative metastases. A critical analysis of completed adjuvant trials will be provided and a framework for the conduct of future trials of adjuvant therapy proposed.