Gastrointestinal Cancer

Educational Objectives

The goal of this program is to improve the surgical management of gastrointestinal cancers. After hearing and assim­ilating this program, the clinician will be better able to:

1.   Identify patients most likely to benefit from surgical resection of esophageal and gastroesophageal tumors.

2.    Utilize presurgical chemotherapy and radiation therapy to increase survival in patients with esophageal and gastroesophageal cancer.

3.    Describe techniques involved in performing a minimally invasive esophagectomy.

4.    Assess whether a patient with gastric cancer is likely to benefit from an extended lymph node dissection.

5.    Discuss recent technologic advances in laparoscopic and robotic gastrectomy procedures.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of in­terest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the faculty and planning committee reported nothing to disclose.

Acknowledgments

Drs. Posner, Ferguson, and Pisters were recorded at 2nd Annual Gastric Cancer Symposium, held October 9, 2009, in Chi­cago, IL, and sponsored by the University of Chicago Center for Gastrointestinal Oncology. The Audio-Digest Foundation thanks the speakers and the University of Chicago Center for Gastrointestinal Oncology for their cooperation in the produc­tion of this program.

Controversies in the Surgical Management of Esophageal and Gastroesophageal Cancer

Mitchell C. Posner, MD, Thomas D. Jones Professor and Vice-Chairman; Chief, Section of General Surgery and Surgical Oncology, Pritzker School of Medicine, University of Chicago, IL

Background on esophageal cancer: incidence and mortality nearly equivalent; treatments require significant im­provement; extent of surgery  —  ie, 1-field dissection, 2-field dissection (abdomen and mediastinum), or 3-field dis­section (abdomen, mediastinum, and cervical region); studies  —large meta-analysis found survival rates with transthoracic esophagectomy (TTE) equivalent to those with transhiatal esophagectomy (THE); randomized phase III trial found TTE with en bloc esophagectomy and 2-field lymph node (LN) resection equivalent to THE in dis­ease-free and overall survival; greater rate of pulmonary complications associated with TTE; 50% lower mortality rates when esophagectomies performed by high-volume surgeons; minimally-invasive esophagectomy  —  data from single institution indicate satisfactory operating time and hospital and intensive care unit (ICU) lengths of stay (LOS; equivalent or inferior to open esophagectomy); may serve as surrogate for cancer surgery with removal of sufficient LNs; requires extraordinary technical expertise; benefits remain unclear (multi-institutional studies ongo­ing)

Role of surgery: speaker attributes recent advances in treatment to combined modality approach (eg, chemotherapy before surgery); patients often intolerant of chemotherapy after procedures; Medical Research Council (MRC) and Intergroup studies  —  evaluated preoperative chemotherapy; conflicting results; positive results in MRC study pos­sibly attributed to higher doses of chemotherapy (increases number of patients eligible for resection); patients non­responsive to upfront chemotherapy experience poorer outcomes; chemotherapy only successful when combined with curative resection (entire tumor removed with negative margins); procedures resulting in gross or microscopic margins showed no benefit; presurgical neoadjuvant chemoradiotherapy (CRT)  —  found superior to surgery alone in meta-analysis; associated with increased mortality in large patient groups (not observed in speaker’s institution); radiation therapy alone vs CRT  —  randomized trial; 5-yr survival rate of 25% in CRT arm (comparable to surgery alone); significant number of patients had residual disease or developed recurrent disease; 50% local failure rate; speaker’s study  —presurgical CRT plus surgery; 30% of subjects achieved 5-yr survival; 60% of survivors showed residual disease in specimens taken during esophagectomy; squamous cell carcinoma (randomized controlled trial)  —>400 patients given CRT; responsive patients randomized to receive surgery or additional CRT; substantial increase in cancer-related deaths among patients without surgery; no difference in overall survival; significant num­ber of patients died in postoperative period (ie, likely due to postsurgical complications); chemotherapy, CRT, and surgery vs chemotherapy plus CRT  —lower incidence of cancer-related deaths in surgery arm, with less local and regional recurrence; 11% postoperative mortality; salvage esophagectomy  —  performed on patients for whom sur­gery not initially planned, in cases of, eg, residual disease or recurrence after CRT; MD Anderson Cancer Center study found operative time and blood loss equivalent to that in patients with CRT and planned surgery

Cancer of gastroesophageal (GE) junction: type I  —esophageal adenocarcinoma (typically with Barrett’s esopha­gus); types II and III  —  gastric carcinomas (without Barrett’s esophagus); patients with type I disease often present with LN disease above diaphragm; with type II or III disease, majority of LN disease occurs below diaphragm; study of types I and II disease above or at cardia level  —  no difference in outcome among abdominothoracic esoph­agectomy, TTE, and total gastrectomy with extension above diaphragm to remove esophagus; D1 (perigastric) vs D2 (extended) LN dissection for type III disease  —  higher mortality rate associated with D2 dissection (highest in hospitals performing procedure infrequently); benefit of postoperative CRT lost in patients who have undergone proper LN dissection

Reconstruction: total esophagectomy  —  elevation of stomach or colon interposition; limited esophagectomy  —elevation of stomach into mediastinum or jejunal interposition; majority of reconstructions after esophagectomy utilize gastric tubes (highly effective); total gastrectomy  —Roux-en-Y considered superior to Billroth II anastomo­sis; meta-analysis found less heartburn and gastric dumping and greater food intake after pouch procedures

MRC’s adjuvant gastric infusional chemotherapy (MAGIC) trial: found chemotherapy before and after surgery su­perior to surgery alone for gastric cancer; higher rate of curative resection among groups receiving chemotherapy (also evident in patients with cancer of GE junction)

Minimally Invasive Surgical Approaches to
Esophageal Cancer

Mark K. Ferguson, MD, Professor, Department of Surgery, Pritzker School of Medicine, University of Chicago, IL

Rationale for minimally invasive esophagectomy (MIE): decreased pain; reduced activation of inflammatory me­diators (possibly associated with better long-term survival); potential for reduced complications and LOS; im­proved completeness of dissection (due to greater visibility, particularly in recurrent laryngeal node region; may improve staging and long-term survival); greater patient acceptance; esophagectomy associated with relatively high rate of postoperative complications; postoperative complications lead to increased hospital mortality, increased LOS in hospital and ICU, and substantial increases in cost of care

Speaker’s technique: typically Ivor Lewis style “2-hole approach” with anastomosis high in chest; “3-hole ap­proach” with anastomosis in neck utilized in select cases; abdominal portion  —  dissect regional LNs; isolate stom­ach while preserving vessels along greater curvature; tubularize stomach; intrathoracic portion  —  place Penrose drain around esophagus from abdominal side (elevates esophagus from esophageal bed); make 2 incisions in pleura (on either side of esophagus) up to arch of azygos vein; dissection stays fairly close to wall of esophagus; regional LNs removed and labeled separately (used in staging); mobilization of esophagus and LN dissection should be completed in 30 to 45 min; dissect azygos vein circumferentially and divide with linear cutting stapler; adequate vi­sualization of recurrent laryngeal nerves and airway necessary; divide pleura up to inlet of thorax; esophagus di­vided circumferentially; vagus nerves and recurrent laryngeal nerves excluded; dissect regional LNs separately after mobilization of esophagus; reconstruction  —most often accomplished via elevation of gastric tube; stump of esophagus anchored to side of stomach; 2 small holes placed in each organ; stapler creates posterior portion of anastomosis and produces “generous” opening (associated with reduced stricturing); reconstruction requires »45 min; chest portion of procedure lasts »2 hr and abdominal portion several hours (MIE does not reduce operating time); supine position during thoracic portion  —  adds challenges and requires single-lung ventilation; however, su­pine positioning causes esophagus to fall naturally from esophageal bed and directs bleeding into anterior pleural space (away from operating field); savings in total operating time likely negated by difficulties in positioning; pre­conditioning of stomach  —dividing left gastric artery laparoscopically improves results of subsequent surgeries by reducing risk for anastomotic leakage; speaker recommends scheduling preconditioning operations 2 to 3 wk be­fore esophagectomy (preserves tissue planes and minimizes scarring)

Adoption of MIE: only 15% of surgical centers worldwide frequently use technique; some centers abandon MIE due to 20% to 30% conversion rate; in speaker’s experience, debriefing after every procedure and associated complica­tion and informing all members of team about changes in technique allowed return to acceptable complication rate; American College of Surgeons Oncology Group attempted to standardize qualifications (publication of results forthcoming); additional training critical (eg, visiting centers of excellence regularly performing procedure); realis­tic benchmarks should distinguish surgeons and institutions qualified to continue operations; MIE has steep learn­ing curve (>50 procedures performed before reaching “expected” complication rates); participation in 100 procedures may be required to achieve competence; clinical advantages of MIE not yet realized due to complica­tion rates; type of MIE performed does not significantly affect outcomes or overall survival; personalization of therapy  —no demonstrated advantage for limiting extent of soft tissue resection, except in  patients with 1A or high-grade dysplasia (eligible for vagal-sparing esophagectomy, which preserves as much soft tissue as possible); personalization of nodal dissection not yet possible (no identified method of sentinel LN mapping); surgeons typi­cally evaluate procedures based on complications; however, patients are often tolerant of complications and care more about long-term quality of life (eg, oxygen dependence and ability to function independently)

Surgical Treatment of Gastric Cancer

Peter W. T. Pisters, MD, Surgical Oncologist, MD Anderson Cancer Center, University of Texas, Houston

Background on gastric cancer: incidence »20,000 cases per year in United States; less coordinated research seen in western countries with decline in gastric cancer rates; increasing amounts of data taken from regions with higher incidence; substantial incidence in eastern Asia and parts of South America along Pacific coast (eg, Chile, Ecuador, Peru); incidence in all of Asia remains high relative to global rates; optimal outcomes achieved through combina­tion of local treatment efficacy and systemic tumor control; benefit of surgery typically dependent on how long dis­ease remains localized (eg, pancreatic adenocarcinoma), effectiveness of systemic therapy (eg, for gastrointestinal stromal tumors), or how safely surgery may be performed (eg, for gastric cancer and pancreatic cancer); patients at risk for peritoneal dissemination, direct metastasis to liver (through portal to systemic circulation), and regional LN metastasis; insufficient ligation may leave residual nodal disease; nodal metastasis common and significantly af­fects prognosis

D1 vs D2 dissection: Dutch study  —  no obvious differences in overall survival; greater mortality associated with ex­tended LN dissection despite highly-skilled instruction; 10% increase in mortality in D2 group (strongly related to increased total mortality among men); substantially better outcomes reported for women undergoing D2 dissection (compared to women undergoing limited dissection); high procedure-related mortality rates may negate therapeutic benefits; high rates of noncompliance with protocols (eg, overdissection in D1 patients or underdissection in D2 pa­tients) complicates analysis of data; Taipei trial  —  221 patients given no adjuvant therapy; single-institution study with small number of surgeons (allows greater quality control); patients receiving extended LN dissection showed unequivocal increases in survival; higher rate of recurrence found in D1 group; D1 dissection may leave positive margins on stomach, residual undissected LNs, or surface disease on capsule of pancreas; randomized data from United States show chemoradiation improves outcomes, but advantages over D2 dissection remain unproven

Patient selection: eligibility determined by assessing endoscopic ultrasonography (EUS) and calculating risk for nodal metastasis (increases with penetration of tumor through gastric wall; highest with transmural disease); crite­ria from Asian investigators  —  recommend D2 operations for patients with ³T2 disease and limited LN involve­ment; risk factors  —  2 Japanese trials found unequivocal increases in complication rates in patients with body mass index (BMI) ³25; even mild cirrhosis may lead to development of uncontrollable ascites and hepatic failure; higher BMI associated with significantly increased rates of anastomotic leak, pancreatic fistula, blood loss, and operating time

Therapeutic use of laparoscopy in foregut: first reported use for management of gastric cancer during 1990s (de­scribed in Asian literature as laparoscopic distal gastrectomy); laparoscopic total gastrectomies with D2 nodal dis­section first performed in late 1990s; Yonsei University (Seoul, Korea)  —  20% of patients undergo laparoscopic or robotic-assisted gastrectomy; due to population screening programs, large numbers of patients receive treatment for early-stage disease; only 5 deaths reported in »900 patients undergoing laparoscopic or robotic procedures; re­sumption of flatus occurred in <3 day; relatively short hospital stays; survival rates comparable to open surgery with stage 1 disease; approach utilizes minimally invasive strategy to replicate open surgical techniques (necessary for systematic LN dissection in requisite regions); anastomosis typically performed extracorporeally; as instrumen­tation improves, intracorporeal anastomosis becomes more feasible; Korean Laparoscopic Gastrointestinal Sur­gery Study (KLASS) group trial  —  ongoing phase III randomized comparison of laparoscopic vs distal open gastrectomy for gastric adenocarcinoma; taken from 16 centers across Korea; substantial surgical quality control; measures traditional end points plus quality of life, inflammatory immune response, and cost-effectiveness; target of 700 patients per arm (1400 total); Western skepticism  —  due to limited incidence of gastric cancer in the West, preparing surgeons to successfully perform totally laparoscopic gastrectomies may prove difficult; D2 dissection arguably provides best local control for gastric adenocarcinoma; surgeon experience and hospital volume important variables; laparoscopic management standard in many Asian surgical centers; adoption in Western centers remains uncertain, but likely to depend on feasibility of sending qualified young surgeons to Asia for training

Suggested Reading

Bedenne L et al: Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102. J Clin Oncol 25:1160, 2007; Decker G et al: Minimally invasive esophagectomy for cancer. Eur J Cardiothorac Surg 35:13, 2009; Fabian T et al: Thoracoscopic esophageal mobilization during minimally invasive esopha­gectomy: a head-to-head comparison of prone versus decubitus positions. Surg Endosc 22:2485, 2008; Gemmill EH, Mc­Culloch P: Systematic review of minimally invasive resection for gastro-oesophageal cancer. Br J Surg 94:1461; Hartgrink HH et al: Extended lymph node dissection for gastric cancer: who may benefit? Final results of the randomized Dutch gastric cancer group trial. J Clin Oncol 22:2069, 2004; Hottenrott C et al: Totally laparoscopic gastrectomy: a real­ity for USA and Europe? Ann Surg Oncol 16:2665, 2009; Hulscher JB, Van Lanschot JJ: Individualised surgical treat­ment of patients with an adenocarcinoma of the distal oesophagus or gastro-oesophageal junction. Dig Surg 22:130, 2005; Kelsen DP et al: Long-term results of RTOG trial 8911 (USA Intergroup 113): a random assignment trial comparison of chemotherapy followed by surgery compared with surgery alone for esophageal cancer. J Clin Oncol 25:3719, 2007; Kodera Y et al: Identification of risk factors for the development of complications following extended and superextended lymphadenectomies for gastric cancer. Br J Surg 92:1103, 2005; Omloo JM et al: Extended transthoracic resection com­pared with limited transhiatal resection for adenocarcinoma of the mid/distal esophagus: five-year survival of a randomized clinical trial. Ann Surg 246:992, 2007; Posner MC et al: Complete 5-year follow-up of a prospective phase II trial of preop­erative chemoradiotherapy for esophageal cancer. Surgery 130:620, 2001; Traverso LW et al: Useful benchmarks to evalu­ate outcomes after esophagectomy and pancreaticoduodenectomy. Am J Surg 187:604, 2004; Wu CW et al: Nodal dissection for patients with gastric cancer: a randomised controlled trial. Lancet Oncol 7:309, 2006.