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.     

Postoperative care after esophagectomy: the surgeon's view

Although in the past esophagectomy was associated with high rates of morbidity and mortality, currently specialized centers have reported reduced hospital death rates of less than 10%. This reduction has been mainly attributed to preoperative patient selection, improvements in anesthesia, surgical techniques, and postoperative care management. In recent years, clinical care pathways, namely physician-directed clinical plans, have been developed to standardize postoperative care after specific surgical procedures: primary goals are improvement in quality of care and reduction in hospital costs. These pathways could be planned after identification of the complications with the highest incidence and the highest hospital costs in order to optimally allocate resources. Aim of this study is to delineate an ideal clinical care pathway after esophagectomy by reporting the most common complications with an overview of advances in perioperative care and providing pointers to what might be achievable.     

Elective surgery for gastrointestinal tumours in the aged

The geriatric population is expanding and clinical decision-making is oftencomplicated by the effects of aging. Age should not be the only parameterconsidered when addressing medical problems. Elderly subjects have been deniedsurgery because of their presumed higher mortality and morbidity. The presentreview summarises the physiology of the aged and discusses operative risks,mortality and morbidity rates as well as therapeutic results for the differentgastrointestinal sites when affected by cancer. Reports on surgical treatmentsare revisited and compared to the same procedures delivered to youngerpatients in the context of the ethical issue of offering the best care toevery patient. Elective operations by surgical oncologists are found to besafe with the exception of major liver resections. Complication rates and meanhospital stay do not differ between the two age groups provided the procedureis conducted with the best-known technique in expert hands. A drop inoperative morbidity has occurred in the past three decades. Severalinvestigators have emphasised the marked increase in morbidity and mortalityexperienced by elderly patients when undergoing emergency procedures.Associated diseases have to be properly assessed, as the aged have a frailphysiologic balance with a reduced capacity for recovery from traumatic eventsincluding major surgical procedures. Careful preoperative evaluation,intraoperative conduct and postoperative care are presently achieved in almostevery major hospital. Good clinical practice is based on the balance betweenprobability of cure and toxic effects. Treatment of the elderly should nolonger be based on untested beliefs and personal opinions. The aged should beaccrued for prospective clinical evaluation and meanwhile should not be deniedoptimal surgical treatment.     

Novel Perspectives for the Treatment of Gastric Cancer: From a Global Approach to a Personalized Strategy

Although recent advances have been made, surgery still remains the mainstay of any curative treatment for gastric cancer patients, with radical gastrectomy representing the procedure of choice. However, patients with locally advanced disease show high rates of locoregional or distant recurrence even after potentially curative resections. According to global results presented in the setting of locally advanced resectable gastric carcinoma, perioperative chemotherapy may be considered a valuable option. On the other hand, clinical trials for advanced gastric cancer seem to suggest that a limit in efficacy has been reached for standard chemotherapy. Interesting data are expected from the development of targeted agents that, similarly to other cancer sites, showed appealing results in gastric cancer as well. Along with new effective therapeutic opportunities, better clinical and molecularly driven patient selection will represent the cornerstone of the global care for these patients.     

Lessons learned from the European thoracic surgery database: The composite performance score

BackgroundThis study reports the methods used to review the Composite Performance Score (CPS) along with a reference table, which will be used in the upcoming ESTS Quality Certification Program.MethodsData from 4303 patients who underwent pulmonary resection (July 2007–January 2010) were captured in the ESTS database and used for the present analysis. Only patients submitted from units contributing at least 100 consecutive lung resections were used for developing the score.According to the best available evidence the following measures were selected for each surgical domain: preoperative care (1. % of DLCO measurement in patients submitted to major anatomic resections; 2. % of preoperative invasive mediastinal staging in patients with clinically suspicious N2 disease), operative care (% of systematic lymph node dissection), outcomes (risk-adjusted cardiopulmonary morbidity and mortality rates). Morbidity and mortality risk-models were developed by logistic regression and validated by bootstrap analyses. Individual processes and outcomes scores were rescaled according to their standard deviations and summed to generate the CPS. Units were rated accordingly and a percentile reference table was produced.ResultsRisk-adjusted survival and absence of morbidity rates varied from 91.5% to 100%, and from 50.2% to 97.5%, respectively. CPS ranged from ?4.038 to 1.24. The 50% percentile of CPS corresponded to 0.404.ConclusionsA revised Composite Performance Score was developed and a reference table presented to be used as a benchmark for the ESTS Quality Certification program.     

Hepatic metastases from colorectal cancer

Over the last 30 years, the benefits of surgical resection and systemic chemotherapy in the management of hepatic metastases from colorectal cancer have been established. Actually, surgical resections are feasible with a very low mortality and a 5-year survival that approaches 50 %, but only 10 % to 20 % of patients are candidate to surgery. The others gain benefit from chemotherapy with more and more active drugs. To improve this overall picture, efforts have been made to increase the number of patients that could be candidates for surgery and to decrease the risk of recurrence after surgical resection. Shrinkage of tumours after administration of preoperative chemotherapy and availability of ablative techniques (radiofrequency and cryotherapy) now permit to treat with curative intent metastases initially considered as non resectable. Chemotherapeutic regimens to decrease the risk of postoperative recurrence are actually tested in clinical trials.     

Approaches to localized pancreatic cancer

Pancreatic cancer is one of the most devastating human malignancies, with a mortality rate that almost equals its incidence rate. In cases of localized pancreatic cancer, surgical resection offers a chance for cure or at least prolonged survival. Adjuvant chemotherapy has been established as the standard of care; prospective, randomized controlled trials have demonstrated a distinct survival benefit of 5-fluorouracil/folinic acid or gemcitabine following surgical resection. More aggressive approaches, including neoadjuvant protocols, venous resections, and extended lymphadenectomy, have been suggested to improve long-term survival. However, based on the available data, there is either no benefit for these approaches or the evidence is not conclusive. Thus, further randomized controlled trials are needed to determine the role of novel therapy regimens in the treatment of pancreatic cancer.     

Updates on Gallbladder Cancer Management

Purpose of Review

We will review the current standard of care management for metastatic gallbladder cancer (GBC), recommendations for resection of incidentally or non-incidentally diagnosed GBC, and developments in preoperative risk stratification and adjuvant chemotherapy.

Recent Findings

Gemcitabine-cisplatin is the standard of care therapy for advanced-stage disease. Patients with incidentally diagnosed GBC should undergo re-resection for T1b, T2, or T3 disease. The presence of residual disease is associated with decreased survival. Diagnostic laparoscopy should be used in select patients to avoid unnecessary laparotomy. Major hepatectomy and common bile duct excision should only be performed in select cases. Current standard of care for adjuvant therapy includes 6 months of oral capecitabine.

Summary

Gallbladder cancer continues to carry high mortality rates due to its aggressive course and early spread. Recent developments in preoperative risk stratification, surgical resection, and chemotherapy have greatly shaped management of this malignancy in the current era.

     

Surgical strategy for bile duct cancer: Advances and current limitations

The aim of this review is to describe recent advances and topics in the surgical management of bile duct cancer. Radical resection with a microscopically negative margin (R0) is the only way to cure cholangiocarcinoma and is associated with marked survival advantages compared to margin-positive resections. Complete resection of the tumor is the surgeon's ultimate aim, and several advances in the surgical treatment for bile duct cancer have been made within the last two decades. Multidetector row computed tomography has emerged as an indispensable diagnostic modality for the precise preoperative evaluation of bile duct cancer, in terms of both longitudinal and vertical tumor invasion. Many meticulous operative procedures have been established, especially extended hepatectomy for hilar cholangiocarcinoma, to achieve a negative resection margin, which is the only prognostic factor under the control of the surgeon. A complete caudate lobectomy and resection of the inferior part of Couinaud's segment IV coupled with right or left hemihepatectomy has become the standard surgical procedure for hilar cholangiocarcinoma, and pylorus-preserving pancreaticoduodenectomy is the first choice for distal bile duct cancer. Limited resection for middle bile duct cancer is indicated for only strictly selected cases. Preoperative treatments including biliary drainage and portal vein embolization are also indicated for only selected patients, especially jaundiced patients anticipating major hepatectomy. Liver transplantation seems ideal for complete resection of bile duct cancer, but the high recurrence rate and decreased patient survival after liver transplant preclude it from being considered standard treatment. Adjuvant chemotherapy and radiotherapy have a potentially crucial role in prolonging survival and controlling local recurrence, but no definite regimen has been established to date. Further evidence is needed to fully define the role of liver transplantation and adjuvant chemo-radiotherapy.     

Multidisciplinary approach in stage III non-small-cell lung cancer: standard of care and open questions

Lung cancer is the most frequent cause of cancer death worldwide and its global incidence has been steadily increasing during recent decades. A third of patients with newly diagnosed non-small-cell lung cancer (NSCLC) present with locally advanced disease. There is not a single widely accepted standard of care for these patients because of the wide spectrum of presentation of the disease. Although feasible and safe in experienced hands, evidence that surgical resection after induction treatment improves overall survival (OS) is lacking. For resectable or potentially resectable stage III, the findings of two phase III trials suggest that surgical resection should not be considered a standard of care but rather reserved for selected patients after critical multidisciplinary assessment, in whom surgery improves survival after downstaging if pneumonectomy can be avoided or in some T4N0-1 resectable tumours. For unresectable stage III NSCLC the standard of care is a combination of chemotherapy and radiotherapy. In those patients with good performance status and minimal weight loss, the concurrent approach has resulted in a statistically significant improvement in OS rates compared with a sequential approach in randomised clinical trials, although several questions remain unresolved.     

Advances in the surgical management of pancreatic cancer

Pancreatic cancer continues to pose a major public health concern and clinical challenge. The incidence of the disease is nearly equivalent to the death rate associated with the diagnosis of pancreatic cancer. Thus, there exists a need for continued improvement in the diagnostic, therapeutic and palliative care of these patients. Surgeons play an integral role in the management of pancreatic cancer patients, with surgery providing the only potentially curative intervention for the disease. Specialized centers have reported improved hospital morbidity, mortality and survival after pancreaticoduodenectomy; however, disease-specific survival after surgical resection remains dismal. An emphasis therefore has been placed upon the accurate preoperative staging of patients in order to identify those patients who would benefit from a complete surgical resection. Surgical staging that incorporates the use of laparoscopic techniques now complements non-surgical methods of staging, including helical CT scans. While there is no defined preoperative staging approach, it is imperative that centers identify areas of expertise and experience with available modalities in any combination to effect accurate staging. Once patients have been accurately staged and deemed resectable, there exist various methods for resection of pancreas lesions, which include the standard "Whipple procedure," pylorus-preserving pancreaticoduodenectomy, regional pancreatectomy, total pancreatectomy, and en bloc vascular resection, where appropriate. Reconstructive techniques have been explored and include methods of pancreaticojejunostomy and pancreaticogastrostomy with or without pancreatic ductal stents and intraoperatively placed closed suction drains. Perioperative mortality following pancreaticoduodenectomy for cancer has a general reported incidence of 1% to 4% at high volume centers experienced with the operation. Morbidity however still remains high with that of delayed gastric emptying, pancreatic anastomotic leak or fistula, intraabdominal abscess, and hemorrhage as the leading reported complications. Researchers have investigated several agents and strategies to decrease or prevent the potential morbidity of these complications including the use of octreotide, drainage of the pancreatic bed and institution of early enteral feeding. Unfortunately, the majority of patients with pancreatic cancer present with either locally advanced or metastatic disease that precludes operative cure. The expected survival for these patients is usually less than six months from diagnosis. Therefore, a goal of therapy should be adequate palliation of symptoms of pain, biliary or duodenal obstruction and improvement of remaining quality of life with the least degree of morbidity possible.     

Preoperative therapy for esophageal cancer: a randomized comparison of chemotherapy versus radiation therapy.

Ninety-six patients with operable epidermoid cancer of the esophagus were entered into a phase III, random assignment study designed to compare the efficacy of two preoperative approaches (chemotherapy [CT] or radiation therapy [RT]). Major study end points were objective response rates, surgical outcome, and recurrence pattern. Patients were randomly assigned to receive either two cycles of cisplatin, vindesine, and bleomycin or 55 Gy of radiation before a planned surgical procedure. Postoperative crossover therapy (radiation to those receiving preoperative CT and vice versa) was given to patients with T3Nany or unresectable tumors. Objective response rates of the primary tumor to preoperative therapy were similar (RT 64%, CT 55%), as were operability rates (RT 77%, CT 75%), resection rates (RT 65%, CT 58%), and operative mortality (RT 13.5%, CT 11.1%). Significantly higher doses of CT could be administered when CT was given as initial therapy, rather than after RT/surgery. Local failure or persistence occurred in 33% of operable patients. The median survival for all patients was 11 months; 20% remain alive without disease (median follow-up, 34 months). Because of the crossover design, it was not possible to analyze survival according to the preoperative therapy arm alone. This study suggests that since CT is as effective in treating local tumor as RT, but can also potentially treat systemic disease, investigational programs using CT before surgery as part of initial treatment for localized esophageal cancer should continue. However, if a significant impact on overall survival is to be achieved, more effective chemotherapy regimens or schedules need to be identified. Outside of carefully designed clinical trials, surgery alone or radiation alone remain standard therapy.     

Chemoprevention of familial adenomatous polyposis

Familial adenomatous polyposis (FAP) has always been first and foremost a surgical disease, whose treatment with colectomy has long been known to reduce risk of premature cancer death. The notion of reducing polyp burden and potentially delaying surgical intervention has spawned a host of “chemoprevention” trials. In this paper I selectively review the findings from these studies, highlighting trial design issues and in particular some of the limitations of historical and existing trial endpoint measures. Nonsteroidal anti-inflammatory agents have been the most commonly employed chemopreventive agents. Sulindac, largely by historical accident, has been the most extensively studied, and is widely considered the standard of care when a clinical decision to intervene medically is made. Newer trials are evaluating combinations of agents in order to take advantage of differing mechanisms of action, in the hope of achieving synergy, as no single agent predictably or completely suppresses adenoma growth. Some of these studies and other single-agent interventions are discussed, though an exploration of the various mechanisms of action is beyond the scope of this paper. It is essential that future trials focus on the issue of “clinical benefit”, not simply because the US Food and Drug Administration has insisted on it, but because only real evidence-based advances can improve the standard of medical care for FAP patients. Hence my focus on issues of trial design and clinically relevant endpoints.     

Review: Malignant tracheo-esophageal fistula: Use of esophageal endoprosthesis

Malignant tracheo-esophageal fistula (TEF) is a serious complication of cancer arising usually in the esophagus, lung, or tracheobronchial tree. Repeated aspiration and pneumonia lead to rapid deterioration and death. The prognosis is dismal and curative resections are curiosities. Surgical bypass of the lesion has been performed but is associated with 25–61% mortality. Other treatments have been employed, such as enterostomies, esophageal endoprostheses, and supportive care. The reported mortality of palliative procedures using endoprostheses, surgical bypass, or exclusion is almost identical. A retrospective review of the data over the past decade revealed a trend toward insertion of endoprostheses. Insertion of endoprostheses can be performed in an endoscopy suite, under sedation, and has fewer major complications than occur with a surgical approach. The periprocedure mortality rate for these patients is 15%, compared to a 29–47% perioperative mortality for patients undergoing surgery. Even so, patients after surgical procedures could survive for 8 months or more, which is better than survival after endoprosthesis intubation. We conclude that insertion of an esophageal endoprosthesis should be the usual preferred option for palliative treatment of malignant TEF. However, for special candidates a surgical procedure is a valid option. © 1996 Wiley-Liss, Inc.     

Preoperative assessment and optimization in periampullary and pancreatic cancer

Perioperative management of pancreatic and periampullary cancer poses a considerable challenge to the pancreatic surgeon, anesthesiologist, and the intensive care team. The preoperative surgical evaluation of a pancreatic lesion aims to define the nature of the lesion (malignant or benign), stage the tumor, and to determine resectability or other non-surgical treatment options. Patients are often elderly and may have significant comorbidities and malnutrition. Obstructive jaundice may lead to coagulopathy, infection, renal dysfunction, and adverse outcomes. Routine preoperative biliary drainage can result in higher complication rates, and metal stents may be preferred over plastic stents in selected patients with resectable disease. Judicious use of antibiotics and maintaining fluid volume preoperatively can reduce the incidence of infection and renal dysfunction, respectively. Perioperative fluid therapy with hemodynamic optimization using minimally invasive monitoring may help improve outcomes. Careful patient selection, appropriate preoperative evaluation and optimization can greatly contribute to a favorable outcome after major pancreatic resections.     

Simultaneous curative resection of double colorectal carcinoma with synchronous bilobar liver metastases

Synchronous colorectal carcinoma (SCRC) indicates more than one primary colorectal carcinoma (CRC) discovered at the time of initial presentation, accounts for 3.1%-3.9% of CRC, and may occur either in the same or in different colorectal segments. The accurate preoperative diagnosis of SCRC is difficult and diagnostic failures may lead to inappropriate treatment and poorer prognosis. SCRC requires colorectal resections tailored to individual patients, based on the number, location, and stage of the tumours, from conventional or extended hemicolectomies to total colectomy or proctocolectomy, when established predisposing conditions exist. The overall perioperative risks of surgery for SCRC seem to be higher than for solitary CRC. Simultaneous colorectal and liver resection represents an appealing surgical strategy in selected patients with CRC and synchronous liver metastases (CRLM), even though the cumulative risks of the two procedures need to be adequately evaluated. Simultaneous resections have the noticeable advantage of avoiding a second laparotomy, give the opportunity of an earlier initiation of adjuvant therapy, and may significantly reduce the hospital costs. Because an increasing number of recent studies have shown good results, with morbidity, perioperative hospitalization, and mortality rates comparable to staged resections, simultaneous procedures can be selectively proposed even in case of complex colorectal resections, including those for SCRC and rectal cancer. However, in patients with multiple bilobar CRLM, major hepatectomies performed simultaneously with colorectal resection have been associated with significant perioperative risks. Conservative or parenchymal-sparing hepatectomies reduce the extent of hepatectomy while preserving oncological radicality, and may represent the best option for selected patients with multiple CRLM involving both liver lobes. Parenchymal-sparing liver resection, instead of major or two-stage hepatectomy for bilobar disease, seemingly reduces the overall operative risk of candidates to simultaneous colorectal and liver resection, and may represent the most appropriate surgical strategy whenever possible, also for patients with advanced SCRC and multiple bilobar liver metastases.     

Hospital volume and hospital mortality for esophagectomy

BACKGROUND: Hospital mortality after esophagectomy has decreased from 29% to 7.5% over the last decades because of improved surgical techniques and better perioperative care. Suggestions have been made that a further decrease in hospital mortality may be achieved by centralization of esophagectomies in high volume centers. METHODS: The effect of hospital volume on hospital mortality after esophagectomy in the Netherlands was analyzed based on data from the Dutch National Medical Registry and the Dutch Network and National Database for Pathology over the period 1993-1998. RESULTS: Annually, approximately 310 (range, 264-321) esophagectomies are performed in the Netherlands. Fifty-two percent are performed in 43-55 low volume centers (1-10 resections a year). Six percent are performed in 1-3 medium volume centers (11-20 resections a year). The remainder (42%) is performed in two high volume centers (> 50 resections a year). Hospital mortality is 12.1%, 7.5% and 4.9% respectively (P < 0.001). The high volume centers seem to see slightly more advanced tumors than the low and medium volume centers. CONCLUSIONS: There is a significant (inverse) relation between hospital mortality and hospital volume for esophageal resection in the Netherlands. Although hospital mortality is not the only measure for quality of care, these data suggest a potential beneficial effect to centralization of esophagectomy in the Netherlands.     

Indications and results of resection for hepatocellular carcinoma.

AIM: In this retrospective series we evaluate our experience in surgical treatment of HCC and examine early and long-term results of 46 hepatic resections. METHODS: Eighty-eight patients with HCC have been observed at our Department. Fifty patients (57%) have been operated, but only 46 (92%) could be resected; 43 patients (93.5%) carried liver cirrhosis. We performed 28 non-anatomical resections (60.8%) and 18 anatomical resections (39.2%). Tumour clearance at resection margin of at least 1cm was considered for a curative resections. RESULTS: Overall mortality and morbidity were 8.7 and 30.4% respectively. These rates significantly decreased in the last years: from 1995 to 2000 no hospital mortality has been recorded. Hospital mortality among non-anatomical and anatomical resection subgroups was 3.5 and 16.6% respectively (P<0.02). After a median f.u. of 41 months, 19 patients (45.2%) had recurrences: it was intrahepatic in 16 (84.4%). We observed a 3-, 5- and 10-years actuarial survival rate 62, 51.1 and 22.5% respectively. Long term survival significantly differed between non-anatomical and anatomical resections, with 5-year and 10-year values of 61.1 and 34.3% vs 37.7 and 18.8% respectively (P=0.0224). CONCLUSIONS: Early results after hepatic resection for HCC can be improved by using a limited surgical approach. Long-term results are still unsatisfactory, because of the high recurrence rate that is not influenced by different surgical approaches.     

A phase II trial of preoperative concurrent radiation therapy and weekly paclitaxel/carboplatin for patients with locally advanced non-small-cell lung cancer

This study was designed to evaluate the efficacy and toxicity of a novel preoperative combined-modality regimen in patients with locally advanced non-small-cell lung cancer (NSCLC). Patients with clinical stage IIB, IIIA, or IIIB NSCLC received preoperative combined-modality therapy with concurrent radiation therapy (RT) and weekly paclitaxel/carboplatin for 5 consecutive weeks. After this treatment, patients believed to have resectable disease by standard surgical criteria underwent thoracotomy. Patients whose disease remained unresectable after initial therapy received further RT with concurrent paclitaxel/carboplatin. Of 107 patients entered into this clinical trial, only 20 patients (19%) were considered to have surgically resectable disease at the time of study entry. Ninety-eight patients (92%) completed preoperative combined-modality therapy. Forty-nine patients (46%) underwent thoracotomy and 34 patients had definitive resection. Fourteen patients (13%) had pathologic complete response (pCR). Thirteen of 18 patients (72%) with clinical stage T3 N0 (IIB) tumors had definitive resections, and 33% had pCR. After a median follow-up of 32 months, the 1- and 2-year actuarial survival rates for the entire group are 64% and 42%, respectively. Favorable-prognosis subgroups included patients who had definitive resection and patients with clinical stage T3 N0 tumors (2-year survival rates of 67% for both subgroups). Preoperative therapy with RT and weekly paclitaxel/carboplatin showed activity in this patient population; however, disease in the majority of patients with extensive involvement of mediastinal nodes remained unresectable after this treatment. Results in patients who initially had unresectable disease do not appear different than results achieved with concurrent RT/chemotherapy approaches. Postoperative complications associated with this preoperative combined-modality regimen were more frequent than expected with resection alone.     

Pancreatic resections: early results and functional behaviour of the stapled pancreatic stump

Pancreaticoduodenectomy is the standard surgical treatment for patients with pancreatic head cancer. Morbidity and mortality rates following this procedure have constantly decreased over the past several years. Leakage of the pancreaticoenteric anastomosis is one of the most serious complications, often responsible for a fatal outcome. Several methods for the management of the pancreatic stump have been described in order to reduce the worrisome incidence of this complication, with variable results. In this series, the Authors review their experience of 75 pancreatic resections and analyze the early results and functional behaviour of 6 patients in which the pancreatic stump was stapled without pancreaticoenteric anastomosis.