Extended lymph node dissection for gastric cancer: who may benefit? Final results of the randomized Dutch gastric cancer group trial.

PURPOSE: The extent of lymph node dissection appropriate for gastric cancer is still under debate. We have conducted a randomized trial to compare the results of a limited (D1) and extended (D2) lymph node dissection in terms of morbidity, mortality, long-term survival and cumulative risk of relapse. We have reviewed the results of our trial after follow-up of more than 10 years. PATIENTS AND METHODS: Between August 1989 and June 1993, 1,078 patients with gastric adenocarcinoma were randomly assigned to undergo a D1 or D2 lymph node dissection. Data were collected prospectively, and patients were followed for more than 10 years. RESULTS: A total of 711 patients (380 in the D1 group and 331 in the D2 group) were treated with curative intent. Morbidity (25% v 43%; P <.001) and mortality (4% v 10%; P =.004) were significantly higher in the D2 dissection group. After 11 years there is no overall difference in survival (30% v 35%; P =.53). Of all subgroups analyzed, only patients with N2 disease may benefit of a D2 dissection. The relative risk ratio for morbidity and mortality is significantly higher than one for D2 dissections, splenectomy, pancreatectomy, and age older than 70 years. CONCLUSION: Overall, extended lymph node dissection as defined in this study generated no long-term survival benefit. The associated higher postoperative mortality offsets its long-term effect in survival. For patients with N2 disease an extended lymph node dissection may offer cure, but it remains difficult to identify patients who have N2 disease. Morbidity and mortality are greatly influenced by the extent of lymph node dissection, pancreatectomy, splenectomy and age. Extended lymph node dissections may be of benefit if morbidity and mortality can be avoided.     

Surgical approaches and outcomes in the treatment of gastric cancer

Resection with extended lymphadenectomy in obtaining local-regional control with negative margins remains the only potentially curative modality in the treatment of gastric cancer. Complete (R0) resections, along with depth of invasion and adequate nodal staging, remain the most important prognostic factors. Because current chemotherapy regimens have limited benefit in advanced disease, the effectiveness of local-regional modalities takes on greater significance. The extent of surgical resection varies with the size, depth, location of the primary tumor, and the stage of disease. Studying patterns of recurrent disease and elucidating the impact of positive margins have led to insights into the biology of the disease and the limitations of local-regional therapies. Considerable controversy surrounds the notion of what defines an adequate lymph node dissection (LND). The recommendation of routine extended (D2) lymphadenectomy (ELND) is difficult to justify based on available randomized studies, but ELND may benefit selected patients when performed by surgeons who can accomplish the dissection with acceptable morbidity/mortality rates. An extended LND results in improved staging, allowing standardization of prognostic factors and survival data worldwide. Patient selection remains critical, limiting the role of surgery in advanced disease and reserving aggressive surgical resection for patients with high curative potential.     

Guidelines for the surgical management of pancreatic adenocarcinoma

Pancreaticoduodenectomy remains the most formidable operative procedure for the surgical treatment of gastrointestinal malignancy. Improved outcomes after the Whipple procedure have been attributed to better preoperative patient selection, advances in three-dimensional radiographic imaging, and regionalization of referrals to high-volume, tertiary care centers. Despite these advances, morbidity and mortality after pancreaticoduodenectomy are not insignificant and the overall prognosis following resection for adenocarcinoma of the pancreas remains poor. Improvements in endoscopic decompression of malignant biliary obstruction have decreased the need for palliative bypass operations and have focused current surgical issues on ways to improve clinical outcomes following potentially curative resections. Controversies such as whether or not to perform extended lymph node dissections, and standard versus pylorus-preserving resections have been addressed by randomized, prospective clinical trials. Major venous resections secondary to local tumor extension are now performed without an increase in morbidity or mortality and with survival rates comparable to standard resections. This has led to even more aggressive resections following neoadjuvant therapy for lesions previously considered unresectable and now perhaps better categorized as borderline resectable. The impact of surgical specialization and regionalization of referrals to tertiary care centers is evident in markedly improved perioperative mortality rates. This article will attempt to describe current guidelines for the preoperative, intraoperative, and postoperative management of patients with localized pancreatic adenocarcinoma.     

Surgical management of pancreatic cancer

The overall prognosis after resection for adenocarcinoma of the pancreas remains poor; however, considerable progress has been made in terms of preoperative patient selection and radiographic staging, refinements in the technical aspects of surgical care, and investigations into the role of multimodality care for patients with potentially curable, resected cancers. Improvements in endoscopic decompression of malignant biliary obstruction have decreased the need for palliative bypass operations and have focused current surgical issues on ways to improve clinical outcomes after potentially curative resections. Controversies such as whether or not to perform extended lymph node dissections and standard versus pylorus-preserving resections have been addressed by randomized, prospective clinical trials. Major venous resections secondary to local tumor extension are now performed without an increase in morbidity or mortality and with survival rates comparable to standard resections. The impact of surgical specialization and regionalization of referrals to tertiary care centers is evident in markedly improved perioperative mortality rates. Neoadjuvant therapy is an area of current clinical investigation. This article describes the current preoperative, intraoperative, and postoperative issues in the surgical management of pancreatic cancer.     

Radical lymph node dissection for gallbladder cancer: indications and limitations

Radical lymph node dissection provides survival benefit for patients with pT2 or more advanced gallbladder carcinoma tumors only if potentially curative resection is feasible; it must always be considered when planning a resection or re-resection for robust patients with pT2 or more advanced gallbladder carcinoma tumors. The degree of radical lymphadenectomy depends on clinically assessed nodal status: portal lymph node dissection is limited to cN0 disease; extended portal nodal dissection is indicated for cN0 and a modest degree of cN1 disease; peripancreatic lymph node dissection with pancreaticoduodenectomy is indicated for selected cases of evident peripancreatic nodal disease and/or direct organ involvement. Extended resection with extensive lymphadenectomy should be limited to expert surgeons because it may cause serious morbidity and mortality.     

Factors influencing outcome in patients undergoing portal vein resection for adenocarcinoma of the pancreas

Background

Survival rates after surgery and adjuvant chemotherapy for pancreatic ductal adenocarcinoma (PDA) remain low. Selected patients with portal/superior mesenteric vein (PV) involvement undergo PV resection at pancreaticoduodenectomy (PD). This study analyses outcomes for PD with/without PV resection in patients with PDA.

Methods

A retrospective analysis of prospectively collected data on patients requiring PD for histologically proven adenocarcinoma between 1/1997 and 9/2009 identified 326 patients with PDA, with 51 requiring PD with PV resection. Patients were analyzed in two groups: PD + PV resection vs. PD alone. Multivariate analysis was used to identify predictive variables influencing survival and the Kaplan-Meier method to estimate patient survival.

Results

Mean age for patients with PV resection was 66.4 (range 46-80) years, 47% were male. Both groups had similar patient demographics, perioperative and tumor characteristics. Postoperative morbidity was similar for patients with and without PV resection (27.5 vs. 28.4%). 30-day mortality was significantly higher in patients with PV resection (13.7%) vs. PD alone (5.1%). Overall survival however was similar in both groups (median PD alone 14.8 months vs. 14.5 months PD + PV). Multivariate analysis identified age, tumor grading, stay on the ICU and lack of chemotherapy as independent risk factors for reduced long-term survival.

Conclusion

In carefully selected patients, PV resection results in similar long-term survival compared to PD alone. In selected patients, PV infiltration may be considered a sign of anatomical proximity of the tumor, rather than only a sign of increased tumor aggressiveness.     

Surgical treatment of pancreatic cancer: Currently debated topics on morbidity,mortality, and lymphadenectomy

This review will examine several aspects of pancreatic surgery. Over the past twenty years, the need for a standardized postoperative complication report after resective pancreatic surgery has led to the definition both of a postoperative complication severity score, a postoperative pancreatic fistula (POPF) severity grading, a fistula risk score (FRS) and a postoperative morbidity index to establish the burden of complications. Unfortunately, three problems have hindered the success of standardization: first, the failure to define a minimum postoperative follow-up period that needs to be reported; second, the lack of a clear definition of POPF-related morbidity and mortality; third, the often-incomplete reporting of postoperative complications. The debate on the extent of lymphadenectomy to associate to pancreaticoduodenectomy started in the late 1980s when, based on retrospective studies, Japanese surgeons reported better survival after extended” than after “standard” lymphadenectomy. Subsequently, eight prospective randomized controlled trials showed that “extended” lymphadenectomy offers no advantage over “standard” lymphadenectomy. Several consensus conference and reviews tried to define the optimal extent of lymphadenectomy to be associated to pancreaticoduodenectomy and distal pancreatectomy (DP). At least nineteen lymph nodes (LN) are required for optimal tumor staging, but eleven LN are considered the minimum to prevent under staging. There is no general agreement about aborting PD in LN16-positive patients; some authors perform PD in fit patients. Based on retrospective studies, a significant increase of R0 resections, a decrease of recurrence rate, a decrease of local recurrence rate and an increase of median or overall disease-free survival were reported after mesopancreas excision.     

Pancreatic Resection for Metastatic Melanoma. Case Report and Review of the Literature

Introduction

Pancreatic metastasis from several malignancies are increasingly encountered in clinical practice, and the usefulness of surgical resection has been suggested for certain neoplasms. Isolated pancreatic metastasis from malignant melanoma is a rare occurrence, and the role of surgery as an adjunct to systemic therapy for melanoma metastatic to a solitary or multiple sites is still debated.

Case Report

We report a patient with melanoma of unknown primary site metastatic simultaneously to the lung and pancreas 3 years after axillary lymph node dissection. Distal pancreatectomy with splenectomy and video thoracoscopic assisted resection of pulmonary metastasis were performed. The postoperative course was uneventful, but 6 months after surgery, the patient experienced single pulmonary recurrence. During chemotherapy with different drugs, pulmonary lesion remained stable for 1 year, and no abdominal recurrence occurred. After then, the size of the lesion progressively increased and a second metastasis occurred in the lung. Five months later, brain metastases occurred, and the patients died 24 months after surgery. Sixteen pancreatic resections for metastatic malignant melanoma, reported with adequate clinical details, were also retrieved from the literature.

Conclusion

In spite of the very limited experience, it appears that surgical resection is only a palliative procedure, because long-term survival is a rare event. However, considering the lack of effective systemic therapy, surgery may be considered as a part of an aggressive multidisciplinary approach in selected cases with malignant melanoma metastatic to single or multiple visceral sites.     

The role of hepatectomy for synchronous liver metastases from pancreatic adenocarcinoma

Background

The role of hepatectomy for patients with liver metastases from ductal adenocarcinoma of the pancreas (PLM) remains controversial. Therefore, the aim of our study was to examine the postoperative morbidity, mortality, and long-term survivals after liver resection for synchronous PLM.

Laparoscopic pancreas- and spleen-preserving D2 lymph node dissection in advanced (cT2) upper-third gastric cancer

BACKGROUND AND OBJECTIVES: Although the laparoscopic assisted total gastrectomy (LATG) has been performed in upper gastric cancer, dissection of lymph nodes No. 10 and 11d without resection of the distal pancreas and the spleen has been hard to accomplish, because of the possibilities of injury to splenic vessels and parenchyma of the spleen or pancreas. Herein, we present successful results in laparoscopic pancreas- and spleen-preserving D2 lymph node dissection in advanced upper gastric cancer. METHODS: Between March 2004 and May 2007, 18 clinical T2 patients who underwent LATG with D2 lymph node dissection for upper gastric cancer were enrolled. RESULTS: We used the technique of encircling and pulling the splenic artery with umbilical tape and that helped us complete dissection of lymph nodes No. 10 and 11d without distal pancreatectomy or splenectomy. The mean operative time was 370 min without any perioperative complications or conversion to an open procedure. CONCLUSIONS: Laparoscopic extended lymph node dissection without pancreatectomy or splenectomy can be adapted to the patients with clinical T2 upper gastric cancer. The techniques like taping of the splenic artery can be a useful tip for surgeons who wish to perform laparoscopic complete D2 lymph node dissection in advanced upper gastric cancer.     

Laparoscopic distal pancreatectomy for adenocarcinoma: safe and reasonable?

As a result of technological advances during the past two decades, surgeons now use minimally invasive surgery (MIS) approaches to pancreatic resection more frequently, yet the role of these approaches for pancreatic ductal adenocarcinoma resections remains uncertain, given the aggressive nature of this malignancy. Although there are no controlled trials comparing MIS technique to open surgical technique, laparoscopic distal pancreatectomy for pancreatic adenocarcinoma is performed with increasing frequency. Data from retrospective studies suggest that perioperative complication profiles between open and laparoscopic distal pancreatectomy are similar, with perhaps lower blood loss and fewer wound infections in the MIS group. Concerning oncologic outcomes, there appear to be no differences in the rate of achieving negative margins or in the number of lymph nodes (LNs) resected when compared to open surgery. There are limited recurrence and survival data on laparoscopic compared to open distal pancreatectomy for pancreatic adenocarcinoma, but in the few studies that assess long term outcomes, recurrence rates and survival outcomes appear similar. Recent studies show that though laparoscopic distal pancreatectomy entails a greater operative cost, the associated shorter length of hospital stay leads to decreased overall cost compared to open procedures. Multiple new technologies are emerging to improve resection of pancreatic cancer. Robotic pancreatectomy is feasible, but there are limited data on robotic resection of pancreatic adenocarcinoma, and outcomes appear similar to laparoscopic approaches. Additionally fluorescence-guided surgery represents a new technology on the horizon that could improve oncologic outcomes after resection of pancreatic adenocarcinoma, though published data thus far are limited to animal models. Overall, MIS distal pancreatectomy appears to be a safe and reasonable approach to treating selected patients with pancreatic ductal adenocarcinoma, though additional studies of long-term oncologic outcomes are merited. We review existing data on MIS distal pancreatectomy for pancreatic ductal adenocarcinoma.     

Routine portal vein resection for pancreatic adenocarcinoma shows no benefit in overall survival

Background

Extended pancreatic resections including resections of the portal (PV) may nowadays be performed safely. Limitations in distinguishing tumor involvement from inflammatory adhesions however lead to portal vein resections (PVR) without evidence of tumor infiltration in the final histopathological examination. The aim of this study was to analyze the impact of these “false negative” resections on operative outcome and long-term survival.

Right hemicolectomy plus pancreaticoduodenectomy vs partial duodenectomy in treatment of locally advanced right colon cancer invading pancreas and/or only duodenum

IntroductionPancreatic or duodenal invasion by locally advanced right colon cancer is an unusual event whose management still represents a surgical challenge. This review aims to compare results of limited vs. extended resection in case of primary right colon cancer invading pancreas and/or duodenum.MethodsA systematic search in Medline, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) was performed. All trials describing the surgical treatment of right colon cancer invading pancreas and/or duodenum were considered. A data extraction sheet was developed, based on the Cochrane Consumers and Communication Review Group's data extraction template.Results5-years overall survival was 52% after en bloc pancreaticoduodenectomy plus right hemicolectomy vs. 0 and 25% in case of duodenal resection with correction by direct suture or pedicled ileal flap, respectively. 30-day postoperative morbidity rate was slightly higher after en block resections (12.8%) with respect to duodenal local resection and direct suture or pedicled ileal flap repair (0 and 12.2%, respectively). After extended resection the rate of pancreatico-jejunal anastomotic leakage was 7.7%.ConclusionsIn patients with right colon cancer extended to the pancreas and/or duodenum surgical multivisceral resection is suggested when complete tumour removal (R0) is achievable. Even though no significant differences in postoperative morbidity and mortality have been shown, 5 y OS has improved in extended resections as compared to duodenal local resection with defect repair either by direct suture or by a pedicled ileal flap.     

贲门癌预后多因素分析和术式对比研究

目的探讨贲门癌的临床特征和影响长期生存的预后因素,评价各种术式及辅助治疗的疗效。方法共收集２６３例贲门癌病例和随访资料,使用Ｌｏｇｉｓｔｉｃ回归和Ｌｏｇ－ｒａｎｋ检验等方法进行生存分析和术式对比研究。结果贲门癌患者男女比例为８．４１,女性平均年龄小于男性。分型中溃疡型、组织学分化程度较低类型比例小。性别、浸润深度、淋巴结受累程度是影响术后生存的预后因子。胃切除范围、淋巴结清扫程度和是否术前化疗,均未显示差异。扩大清扫术后并发症率高于一般清扫,而死亡率无差异。对于Ⅲ期Ｎ０～１患者,扩大清扫术后长期生存优于一般根治手术。结论贲门癌有独特的临床特征,治疗中应根据预后因子进行治疗方案的调整。对于较早期患者,推荐使用扩大清扫术。     

Radical pancreatectomy for ductal cell carcinoma of the head of the pancreas

Seventy-four patients were treated with a radical or a nonradical pancreatectomy for ductal cell carcinoma of the head of the pancreas. Their survival rates and the selection of the operative procedure were evaluated. In 32 patients, a radical pancreatectomy was attempted where there was sufficient clearance of regional or juxta-regional lymph nodes beyond the group of suspected metastatic nodes, as well as a resection of a greater margin of soft tissue around the pancreas. These patients' cumulative 5-year survival rate was 33.4%. In 14 Stage I or Stage II patients, the cumulative 5-year survival rate was 46.4%. In 18 Stage III or Stage IV patients, the cumulative 5-year survival rate was 20.7%. For 42 patients treated with a nonradical pancreatectomy with the dissection of lymph nodes adjacent to the pancreas or of regional lymph nodes but with insufficient clearance of the soft tissue around the pancreas, the cumulative 2-year and 3-year survival rates were 5.4% and 0%, respectively. In seven patients with Stage II carcinoma, the survival rate was 16.7% after 2 years and 0% after three years. In 35 Stage III or Stage IV patients, the survival rate was 3.2% after 2 years and 0% after 3 years. Thus, the survival rates were significantly higher in patients treated with radical operation than in patients who had nonradical operation. These results indicate that a radical pancreatectomy with sufficient lymph node clearance with the surrounding connective tissue around the pancreas is indispensable to cure patients with ductal cell carcinoma of the pancreas.     

Sentinel lymph node navigation surgery for pancreatic head cancers

Recently, sentinel lymph node (SN) concept has been validated for gastrointestinal and breast cancers. Our previous study has shown that the No. 13 posterior pancreaticoduodenal lymph node group constitutes the major regional drainage site from primary tumors in the pancreatic head, and that the status of these nodes predicts that of the No. 16 abdominal paraaortic lymph node group. Based on these results, we have developed SN navigation surgery for pancreatic cancer, in the search for more curable and less invasive surgery. In brief, 2% patent blue dye is injected into the peritumoral area. Approximately 5 min later, one or more blue-stained nodes within the area of the No. 13 lymph node group are identified and excised for intraoperative frozen section examination. The subsequent surgical decision-tree is as follows: i) if No. 13 SNs are negative, an extended No. 16 lymph node dissection is not performed to reduce morbidity, and ii) when cancer is found, the No. 16 lymph nodes are dissected completely. Since July 1997, nine of 21 patients scheduled to undergo an extended curative surgery underwent SN biopsy. SNs within the area of the No. 13 lymph node group were identified in 8 (89%) patients. An extended No. 16 lymph node dissection was avoided in 4 SN-negative patients. The overall 3-year survival rate of the 21 patients was 36%, and 4 patients (three SN-negative and one SN-positive patients) with stage IVa disease were alive 3 years after surgery. Three SN-negative patients underwent an extended curative pylorus-preserving pancreaticoduodenectomy (PpPD) with combined portal vein resection, but without an extended No. 16 dissection. In conclusion, SN biopsy and curative PpPD can increase curability, reduce morbidity, and provide long-term survival in patients with locally advanced pancreatic head cancer as an alternative to routine extended No. 16 lymph node dissection.     

Strategies to improve local control of resected pancreas adenocarcinoma

Background

Only approximately one in ten pancreas cancer patients is a candidate for potentially curative resection of this disease. Even this small fraction of patients has a poor prognosis following pancreatico-duodenectomy. The disease has an anatomic location that makes it difficult for the surgeon to maintain adequate margins of resection and prevent tumor spillage at the time of resection. Also, the disease is biologically aggressive and even with a complete visible resection of the disease, micrometastases are likely to remain behind.

扩大淋巴结清扫对胰头癌患者预后效果的观察

目的 探讨扩大淋巴结清扫对胰头癌患者疗效及预后的影响.方法 回顾性分析136例胰头癌患者的临床资料,根据治疗方法的不同将患者分为扩大组和常规组,每组各68例.常规组患者接受胰十二指肠切除术及常规淋巴结清扫,扩大组患者接受胰十二指肠切除术及扩大淋巴结清扫.比较两组患者的术中、术后指标及并发症发生率.结果 扩大组患者的手术时间长于常规组,术中出血量多于常规组(P﹤0.05).扩大组患者术后胃排空延迟的发生率高于常规组,阳性淋巴结检出数多于常规组,原位癌复发率低于常规组,差异均有统计学意义(P﹤0.05).术后两组患者吻合口瘘、腹腔出血及腹腔感染的发生率比较,差异均无统计学意义(P﹥0.05).随访5~33个月,两组患者的中位生存时间比较,差异无统计学意义(P﹥0.05).结论 对于行胰十二指肠切除术的胰头癌患者,扩大淋巴结清扫范围可提高阳性淋巴结检出率,降低原位癌复发率,但对患者的远期疗效无明显影响,同时加重了对患者机体的损伤,延长了手术时间,增加了术中出血量及胃排空延迟的发生率,不建议常规对患者采用扩大淋巴结清扫术,尤其是年老及身体状况较差者.     

Status of extended lymph node dissection: locoregional control is the only way to survive gastric cancer

There are many factors that are of influence on gastric cancer treatment. The only way to survive is complete locoregional control. More extended dissections should lead to better outcome, but increased morbidity and mortality probably offset its long-term effect in survival in randomised studies. In this article the factors of influence on outcome of gastric cancer treatment such as the extent of lymph node dissection, splenectomy, pancreatectomy, age, volume and additional treatments are discussed. A literature review of these factors in relation to the latest results of the Dutch Gastric Cancer Trials are presented. If morbidity and mortality can be reduced there might be an advantage of extended lymph node dissection. Splenectomy and pancreatectomy should be performed only in case of direct in growth from the tumour into these organs. Centralisation of gastric cancer treatment should be achieved in order to improve results and to facilitate research. By refining selection criteria in the treatment of gastric cancer further improvements are to be expected.