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Self-Help and Mutual Aid Groups: International and Multicultural Per¬ spectives lives up to its ambitious title. The chapter articles, developed from presentations made at the September 1992 International Conference on SelfHelp/Mutual Aid in Ottawa, Ontario, es¬ tablish a framework for international analysis of the universal and particular attributes of self-help and begin to fill in some of the spaces in that framework. The authors grapple with expanding the definitional issues occupying research¬

Publication of your research represents the culmination of your scientific activities. The key to getting manuscripts accepted is to make them understandable and informative so that your colleagues will read and benefit from them. We describe key criteria for acceptance of manuscripts and outline a multi-step process for writing the manuscript. The likelihood that a manuscript will be accepted by a major journal is significantly increased if the manuscript is written in polished and fluent scientific English. Although scientific quality is the most important consideration, clear and concise writing often makes the difference between acceptance and rejection. As with any skill, efficient writing of high-quality manuscripts comes with experience and repetition. It is very uncommon for a manuscript to be accepted as submitted to a journal. Thoughtful and respectful responses to the journal reviewers' comments are critical. Success in scientific writing, as in surgery, is dependent on effort, repetition, and commitment. The transfer of knowledge through a well-written publication in a high-quality medical journal will have an impact not only in your own institution and country, but also throughout the world.

The Annals of Surgical Oncology is in its 17 year of publication. As the journal has matured, it has become the most cited surgical oncology journal published and has been adopted as the venue for communicating new knowledge by surgeons all over the world. Manuscript submissions have increased by 65% between 2007 and 2009, the majority (70%) of which now originate from outside the United States (Fig. 1). The Annals is also the primary resource for surgeons practicing in the United States, both in academic and community practice settings, because it is read by all members of the Society of Surgical Oncology (the majority of whom are in an academic practice) and the American Society of Breast Surgeons (the majority of whom are in a community-based practice). The Annals has also become an official journal with surgical and oncology societies in Europe, Latin America, and Africa. Thus, the readership and authorship constituency of the Annals of Surgical Oncology now reaches across the globe—both in print and electronically— for surgeons treating patients with cancer. The scientific value of the journal is benchmarked with the Science Citation index. We are pleased to report that the journal’s impact factor has increased almost 2 points to 4.13, and the journal is now ranked 6th out of 166 surgery journals (Fig. 2, Table 1). This increase in impact is significant because it occurred despite an increased number of published pages from 2006 to 2007 (1753 vs 3637 printed pages), a variable that can push a journal’s measured impact downward by expanding the denominator. Since the number of published pages remained stable over the past 2 years, we are hopeful that the impact factor will continue to increase. During 2009, articles published in the Annals of Surgical Oncology in 2007 and 2008 were cited in 3527 articles published in the literature. Given the growth of highquality papers published in the journal, the impressive volume of citations in recently published articles reflects the scholastic influence of Annals articles on the field of surgical oncology, both in the clinical and the research spheres. The editorial leadership of the journal is also broadened to reflect the leadership of cancer surgeons not only in the United States, but also around the globe. The 2010–2011 Editorial Board roster, available online and in the front of this issue, displays the new and continuing Editorial Board members as well as two new subgroups—International Associate Editors and the Latin American Scientific Advisory Board. The addition of these international leaders to the journal reflects the increase visibility, usage, and citations of ASO worldwide. We are also pleased to formally welcome Suzanne Klimberg, MD, to her new role as Deputy Editor of the journal; in this position, Suzanne is leading the journal as it becomes positioned to be an explicit educational resource for Maintenance of Certification. Dr. Eric Whitacre and colleagues have successfully piloted the Mastery of Breast Surgery, which is a case log system focused on three outcome measures specific to breast. This log qualifies for MOC Part IV and recently has been ‘‘linked’’ to the ASO to aid in obtaining credit for Part II. The SSO has appointed a committee to develop other venues for the surgical oncologist that includes Drs. Clifford Ko, Jeff Gershenwald, Doug Tyler, and Suzanne Klimberg. They hope to pilot a similar model for the American College of Surgeon Case log in five cancer areas with content specialist in each area. Society of Surgical Oncology 2010

Purpose Although chemoradiotherapy plus resection is considered standard treatment for operable rectal carcinoma, the optimal time to administer this therapy is not clear. The NSABP R-03 (National Surgical Adjuvant Breast and Bowel Project R-03) trial compared neoadjuvant versus adjuvant chemoradiotherapy in the treatment of locally advanced rectal carcinoma. Patients and Methods Patients with clinical T3 or T4 or node-positive rectal cancer were randomly assigned to preoperative or postoperative chemoradiotherapy. Chemotherapy consisted of fluorouracil and leucovorin with 45 Gy in 25 fractions with a 5.40-Gy boost within the original margins of treatment. In the preoperative group, surgery was performed within 8 weeks after completion of radiotherapy. In the postoperative group, chemotherapy began after recovery from surgery but no later than 4 weeks after surgery. The primary end points were disease-free survival (DFS) and overall survival (OS). Results From August 1993 to June 1999, 267 patients were randomly assigned to NSABP R-03. The intended sample size was 900 patients. Excluding 11 ineligible and two eligible patients without follow-up data, the analysis used data on 123 patients randomly assigned to preoperative and 131 to postoperative chemoradiotherapy. Surviving patients were observed for a median of 8.4 years. The 5-year DFS for preoperative patients was 64.7% v 53.4% for postoperative patients (P = .011). The 5-year OS for preoperative patients was 74.5% v 65.6% for postoperative patients (P = .065). A complete pathologic response was achieved in 15% of preoperative patients. No preoperative patient with a complete pathologic response has had a recurrence. Conclusion Preoperative chemoradiotherapy, compared with postoperative chemoradiotherapy, significantly improved DFS and showed a trend toward improved OS.

Purpose Most patients with colorectal liver metastases present to general surgeons and oncologists without a specialist interest in their management. Since treatment strategy is frequently dependent on the response to earlier treatments, our aim was to create a therapeutic decision model identifying appropriate procedure sequences. Methods We used the RAND Corporation/University of California, Los Angeles Appropriateness Method (RAM) assessing strategies of resection, local ablation and chemotherapy. After a comprehensive literature review, an expert panel rated appropriateness of each treatment option for a total of 1,872 ratings decisions in 252 cases. A decision model was constructed, consensus measured and results validated using 48 virtual cases, and 34 real cases with known outcomes. Results Consensus was achieved with overall agreement rates of 93.4 to 99.1%. Absolute resection contraindications included unresectable extrahepatic disease, more than 70% liver involvement, liver failure, and being surgically unfit. Factors not influencing treatment strategy were age, primary tumor stage, timing of metastases detection, past blood transfusion, liver resection type, pre-resection carcinoembryonic antigen (CEA), and previous hepatectomy. Immediate resection was appropriate with adequate radiologically-defined resection margins and no portal adenopathy; other factors included presence of ≤ 4 or > 4 metastases and unilobar or bilobar involvement. Resection was appropriate postchemotherapy, independent of tumor response in the case of ≤ 4 metastases and unilobar liver involvement. Resection was appropriate only for > 4 metastases or bilobar liver involvement, after tumor shrinkage with chemotherapy. When possible, resection was preferred to local ablation. Conclusion The results were incorporated into a decision matrix, creating a computer program (OncoSurge). This model identifies individual patient resectability, recommending optimal treatment strategies. It may also be used for medical education.

At the Society of Surgical Oncology (SSO) Executive Council meeting on June 27, 1992, the Chair of the Publications Committee, Dr. Robert Beart, reported on the Society’s efforts to start its own surgical oncology journal. Drs. Beart and David P. Winchester proposed a motion to authorize the SSO to publish a bimonthly oncology journal. The Executive Council authorized Drs. Charles Balch (President) and Donald Morton (President-Elect) to appoint a Search Committee of three to four members, to be chaired by Dr. Robert Beart, to solicit and interview potential candidates for the Society’s new journal. At the SSO Executive Council meeting on October 13, 1992, Drs. David P. Winchester and Kirby Bland proposed and passed a motion to name the new SSO journal the Annals of Surgical Oncology. The Executive Council then unanimously appointed Dr. Charles Balch to the position of Editor-in-Chief of the Annals of Surgical Oncology and Drs. Donald Morton and Edward Copeland III as Associate Editors. Dr. Mark Roh was appointed as Assistant Editor until 1997, when he was appointed as Executive Editor. In 2010, Dr. Suzanne Klimberg was appointed as a Deputy Editor of the journal, with primary responsibilities in coordinating the educational and Continuing Medical Education functions of the journal, as well as serving as the journal’s liaison with the newly created American Board of Surgical Oncology.

Purpose The optimal chemotherapy regimen administered concurrently with preoperative radiation therapy (RT) for patients with rectal cancer is unknown. National Surgical Adjuvant Breast and Bowel Project trial R-04 compared four chemotherapy regimens administered concomitantly with RT. Patients and Methods Patients with clinical stage II or III rectal cancer who were undergoing preoperative RT (45 Gy in 25 fractions over 5 weeks plus a boost of 5.4 Gy to 10.8 Gy in three to six daily fractions) were randomly assigned to one of the following chemotherapy regimens: continuous intravenous infusional fluorouracil (CVI FU; 225 mg/m2, 5 days per week), with or without intravenous oxaliplatin (50 mg/m2 once per week for 5 weeks) or oral capecitabine (825 mg/m2 twice per day, 5 days per week), with or without oxaliplatin (50 mg/m2 once per week for 5 weeks). Before random assignment, the surgeon indicated whether the patient was eligible for sphincter-sparing surgery based on clinical staging. The surgical end points were complete pathologic response (pCR), sphincter-sparing surgery, and surgical downstaging (conversion to sphincter-sparing surgery). Results From September 2004 to August 2010, 1,608 patients were randomly assigned. No significant differences in the rates of pCR, sphincter-sparing surgery, or surgical downstaging were identified between the CVI FU and capecitabine regimens or between the two regimens with or without oxaliplatin. Patients treated with oxaliplatin experienced significantly more grade 3 or 4 diarrhea (P < .001). Conclusion Administering capecitabine with preoperative RT achieved similar rates of pCR, sphincter-sparing surgery, and surgical downstaging compared with CVI FU. Adding oxaliplatin did not improve surgical outcomes but added significant toxicity. The definitive analysis of local tumor control, disease-free survival, and overall survival will be performed when the protocol-specified number of events has occurred.

We begin this first issue of 2010 by welcoming the 3,000 members of the American Society of Breast Surgeons and assessing the growth of the Annals of Surgical Oncology. The Annals is now the official journal for both the Society of Surgical Oncology and the American Society of Breast Surgeons (ASBS). The ASBS brings with it a membership whose mission aligns nicely with the strategic vision of the Society of Surgical Oncology (SSO) and the Annals. The ASBS will have a special ASO edition to be published in October 2010, which will be a valuable additional resource for both ASBS members and SSO members. The growth of the Annals, both in size and content, has been impressive! Over the last 5 years, submissions and resubmissions of original work have almost tripled (approximately 600 articles submitted in 2005–2006 vs. more than 1600 in 2008–2009). The number of reviewers volunteering their critical expertise to the peer review process grew from 750 in 2006 to over 2000 experts in 2009, with an average number of reviews completed per reviewer declining from 2.5 to 1.6. This growth in the number of peer review experts and the range in their expertise reflects the journal’s continuing expansion of breadth, depth, and range of subject matter. We thank them for their voluntary effort that shapes the scientific excellence of the journal. The Annals now covers 18 content areas, as reflected in the structure of the Editorial Board (Table 1). New additions in 2009 include a section on Colorectal Cancer led by Heidi Nelson, MD, and an expansion of Translational Research to include Biomarkers, led by James Cusack, MD. The journal continues to be especially strong in Hepatobiliary and Pancreatic Tumor papers, now broken into two distinct groups led by Michael Choti, MD, and Andrew Lowy, MD, respectively. Gastrointestinal, Melanoma, and Breast Oncology sections continue to grow as well. Table 1 2009–2010 Editorial Board sections and section editors

Background: The goal of this study was to determine if staging with intraoperative ultrasound (IOUS), assessment of porta hepatis lymph nodes, and evaluation of resection margins can improve selection of patients likely to benefit from resection of colorectal liver metastases. Methods: A retrospective evaluation was performed on patients undergoing celiotomy with intent to resect colorectal liver metastases. Patients were considered unresectable if extrahepatic disease was identified by peritoneal exploration or if IOUS demonstated greater than four lesions or the inability to achieve negative margins. Tumor-negative margins were confirmed by pathologic evaluation. Actuarial 5-year survival was calculated using the method of Kaplan and Meier. Results: Median follow-up is 25 months. Of the 151 patients undergoing operative exploration, 107 (71.0%) underwent liver resection (all margins tumor negative). Three operative deaths occurred in this group (2.8%). The disease of 30 patients (19.8%) was considered unresectable due to extrahepatic involvement, and that of 14 patients (9.2%) was demonstrated by IOUS to be unresectable. Five-year actuarial survival was 44% for the resected group and 0% for the unresectable patients (p

Antibody LiCO 16.88 is a human IgM recognizing a 30- to 45-kDa intracytoplasmic antigen present in human adenocarcinoma cells. An 8-mg sample of antibody labeled with 5 mCi131I was co-administered i. v. with 120 mg (three patients), 240 mg (three patients) or 480 mg (four patients) unlabeled antibody as a 4-h infusion. The plasma half-life was 24±1.2 h and the immediate apparent volume of distribution was 5.2±0.2 l at the 28-mg dose level. The plasma half-lives and the cumulative urinary excretion of radiolabel did not seem to vary significantly with increasing doses of unlabeled antibody. However, both the volume of distribution and the clearance rate from plasma increased significantly with increasing antibody dose. Uptake of antibody into tumor tissues obtained during laparotomy 8–9 days after administration varied between 0.00002% ID/g and 0.00127% ID/g. In five of seven patients, the tumor content of antibody was higher than that in adjacent normal tissue. Tumor-to-normal tissue ratios ranged from 0.8 to 10 ( $$\bar x$$ =3.8±1.0). In general, the higher radioactivity(cpm)/g tumor was confirmed by both immunoperoxidase and autoradiography. Antibody 16.88 localizes in tumors after administration and may be considered for use in radioimmunotherapy trials.

Activation of the tyrosine kinase of the c-src gene product, pp60c-src, has been shown to occur in nearly every primary colorectal carcinoma, and is found as early as in polyps of high malignant potential. However, no studies have addressed potential pp60c-src changes which occur during progression. To examine this question, we have studied kinase activity and protein levels in 7 colonic polyps, 19 primary lesions, and 19 liver metastases relative to normal colonic mucosa. Significant increases in tyrosine kinase activity were seen as early as in colonic polyps of high malignant potential. Further increases were observed in activity and level in primary tumors. However, the greatest increases in activity and protein levels were observed in liver metastases. Additionally, six metastatic lesions were obtained in which synchronous primary tumor was resected. In each of these liver metastases, pp60c-src activity and level were significantly increased relative to the corresponding primary tumor, as well as to normal colonic mucosa. Our results demonstrate that progression of colon primary tumors to liver metastases correlates with increased pp60c-src kinase activity and protein level.

Purpose Prior trials have shown that surgery followed by hepatic artery infusion (HAI) of floxuridine (FUDR) alternating with systemic fluorouracil improves survival rates. Oxaliplatin combined with capecitabine has demonstrated activity in advanced colorectal cancer. Based on this observation a trial was conducted to assess the potential benefit of systemic oxaliplatin and capecitabine alternating with HAI of FUDR. The primary end point was 2-year survival. Patients and Methods Patients with liver-only metastases from colorectal cancer amenable to resection or cryoablation were eligible. HAI and systemic therapy was initiated after metastasectomy. Alternating courses of HAI consisted of 0.2 mg/m2/d FUDR and dexamethasone, day 1 through 14 weeks 1 and 2. Systemic therapy included oxaliplatin 130 mg/m2 day 1 with capecitabine at 1,000 mg/m2 twice daily, days 1 through 14, weeks 4 and 5. Two additional 3-week courses of systemic therapy were given. Capecitabine was reduced to 850 mg/m2 twice daily after interim review of toxicity. Results Fifty-five of 76 eligible patients were able to initiate protocol-directed therapy and completed median of six cycles (range, one to six). Three postoperative or treatment-related deaths were reported. Overall, 88% of evaluable patients were alive at 2 years. With a median follow-up of 4.8 years, a total of 30 patients have had disease recurrence, 11 involving the liver. Median disease-free survival was 32.7 months. Conclusion Alternating HAI of FUDR and systemic capecitabine and oxaliplatin met the prespecified end point of higher than 85% survival at 2 years and was clinically tolerable. However, the merits of this approach need to be established with a phase III trial.

Patients with locoregional gastric carcinoma often die because of the low rates of curative resection and frequent appearance of distant metastases (mainly peritoneal and hepatic). To evaluate the feasibility of preoperative and postoperative chemotherapy, 25 consecutive previously untreated patients with potentially resectable locoregional gastric carcinoma received two preoperative and three postoperative courses of etoposide, 5-fluorouracil, and cisplatin (EFP). Ninety-eight courses (median, five courses; range, two to five courses) were administered. Six patients had major responses to EFP. Eighteen patients (72%) had curative resections, and three specimens (12%) contained only microscopic carcinoma. At a median follow-up of 25 months, the median survival of 25 patients was 15 months (range, 4 to 32+ months). Peritoneal carcinomatosis was the most common indication of failure. One patient died of postoperative complications, but there were no deaths due to chemotherapy. EFP-induced toxic reactions were moderate. Preoperative and postoperative chemotherapy for locoregional gastric carcinoma is feasible, and additional studies to develop regimens that could result in 5% to 10% complete pathologic responses may be warranted.

Colorectal liver metastases are a common clinical problem and require more effective therapy. Kupffer cells (KC) perform many important homeostatic functions within the liver and may also possess the ability to mediate tumor cytotoxicity. We investigated the ability of human KC to mediate cytotoxicity against human colon adenocarcinoma targets (HT 29) in vitro. Unstimulated human KC were cytotoxic against the HT 29 targets at all effector/target ratios tested. This cytotoxicity was increased significantly (p < 0.05) when the KC were stimulated with interferon-γ and lipopolysaccharide. Human KC produced tumor necrosis factor (TNF), and KC stimulation significantly (p < 0.05) increased secretion of this monokine. The addition of anti-TNF antibody to the KC-HT 29 cocultures completely neutralized all of the available TNF yet cytotoxicity was not affected, suggesting the participation of a membrane-bound form of TNF or other mechanisms.

Long term hepatic artery chemotherapy for metastatic disease to the liver has been made practical by technologic advances in pumps and catheters. The surgical placement of these pumps and catheters can be associated with a significant morbidity unless careful attention is given to variations in hepatic arterial anatomy and to eliminating collateral arterial supply to the distal stomach and duodenum. Gastroduodenal devascularization should be performed in all patients and should be confirmed both with intra-operative fluorescein injection and postoperative scintigraphy scanning. Routine cholecystectomy avoids the complication of chemical cholecystitis. Exact placement of the catheter tip at the junction of the gastroduodenal artery and the hepatic artery with fixation of the catheter in this position by placement of bidirectional ligatures around the catheter bead will reduce the incidence of hepatic artery thrombosis and catheter migration. Intrahepatic arterial collateralization in most patients allows for ligation of variant lobar vessels with total liver perfusion through the remaining lobar arterial supply. This again can be confirmed intra-operatively with fluorescein injection and postoperatively with scintigraphy scanning. Strict attention to these technical details will allow continued use of this important therapeutic modality in the treatment of hepatic metastases and by minimizing surgical complications will encourage continued trials to improve the efficacy of long term hepatic arterial chemotherapy.

Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, Texas 77030-4009, USA Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan Department of Interventional Radiology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, Texas 77030-4009, USA Division of Gastroenterologic and General Surgery, Mayo Clinic, RochesterMinnesota, USA Department of Surgery, The University of Hong Kong, Medical, Centre Queen Mary Hospital, Hong Kong, China Liver Surgery Unit, Third Department of Surgery, University School of Medicine, Istituto Clinico Humanitas IRCCS, Rozzano, Milan, Italy Department of Radiology, Hopital Beaujon, Clichy, France Department of Surgery, Drexel University College of Medicine, Allegheny General Hospital, Pittsburgh, Pennsylvania, USA

National Surgical Adjuvant Breast and Bowel Project R-04 was designed to determine whether the oral fluoropyrimidine capecitabine could be substituted for continuous infusion 5-FU in the curative setting of stage II/III rectal cancer during neoadjuvant radiation therapy and whether the addition of oxaliplatin could further enhance the activity of fluoropyrimidine-sensitized radiation.Patients with clinical stage II or III rectal cancer undergoing preoperative radiation were randomly assigned to one of four chemotherapy regimens in a 2x2 design: CVI 5-FU or oral capecitabine with or without oxaliplatin. The primary endpoint was local-regional tumor control. Time-to-event endpoint distributions were estimated using the Kaplan-Meier method. Hazard ratios were estimated from Cox proportional hazard models. All statistical tests were two-sided.Among 1608 randomized patients there were no statistically significant differences between regimens using 5-FU vs capecitabine in three-year local-regional tumor event rates (11.2% vs 11.8%), 5-year DFS (66.4% vs 67.7%), or 5-year OS (79.9% vs 80.8%); or for oxaliplatin vs no oxaliplatin for the three endpoints of local-regional events, DFS, and OS (11.2% vs 12.1%, 69.2% vs 64.2%, and 81.3% vs 79.0%). The addition of oxaliplatin was associated with statistically significantly more overall and grade 3-4 diarrhea (P.0001). Three-year rates of local-regional recurrence among patients who underwent R0 resection ranged from 3.1 to 5.1% depending on the study arm.Continuous infusion 5-FU produced outcomes for local-regional control, DFS, and OS similar to those obtained with oral capecitabine combined with radiation. This study establishes capecitabine as a standard of care in the pre-operative rectal setting. Oxaliplatin did not improve the local-regional failure rate, DFS, or OS for any patient risk group but did add considerable toxicity.

US Department of Agriculture, Agricultural Research Service, National Arboretum, Floral and Nursery Plants Research Unit, Beltsville, MD 20705, USA US Department of Agriculture, Agricultural Research Service, National Germplasm Resources Laboratory, Plant Disease Research Unit, Beltsville, MD 0705, USA Seoul National University, CALS, NICEM, San 56-1 Sillim-9-dong Gwanak-gu, Seoul 151-921, Republic of Korea Cheonnam National University, School of Biological Science & Technology, Gwangju 500-757, Republic of Korea

Evaluation and treatment of patients with hepatocellular carcinoma is dependent on accurate staging. Tumor-specific factors and the degree of underlying liver disease must be considered when evaluating patients with hepatocellular carcinoma. Clinical staging classification systems based on preinterventional data are predictive of survival and influence patient selection for various therapeutic modalities. Pathologic staging systems accurately assess prognosis and influence additional treatment post resection. The various staging systems for hepatocellular carcinoma are reviewed in detail. The benefits and limitations of these classification systems are discussed in this review. Considerable controversy remains over which classification system provides the optimum staging of hepatocellular carcinoma. The revised American Joint Committee on Cancer/International Union Against Cancer emphasizes the importance of major vascular and microvascular invasion as independent predictors of death and the negative impact of severe fibrosis/cirrhosis on survival following resection of hepatocellular carcinoma. As such, it is currently the most accurate staging system in this group of patients. Its applicability in those patients who are not candidates for resection is uncertain.

Background: Metastatic breast cancer is generally believed to be associated with a poor prognosis. Therapeutic advances over the past two decades, however, have resulted in improved outcomes for selected patients with limited metastatic disease. Methods: Between March 1991 and October 2002, 31 patients had hepatic resection for breast cancer metastases limited to the liver. Clinical and pathologic data were collected prospectively from breast and hepatobiliary databases. Results: Median age of patients was 46 years (range, 31 to 70). Liver metastases were solitary in 20 patients and multiple in 11 patients. Median size of the largest liver metastasis was 2.9 cm (range, 1 to 8). Major liver resections (three or more segments resected) were performed in 14 patients, whereas minor resections (fewer than three segments resected) with or without radiofrequency ablation (RFA) were performed in 17 patients. No postoperative mortality occurred. Of the 31 patients, 27 (87%) received either preoperative or postoperative systemic therapy as treatment for metastatic disease. The median survival was 63 months; a single patient died within 12 months of hepatic resection. The overall 2- and 5-year survival rates were 86% and 61%, respectively, whereas the 2- and 5-year disease-free survival rates were 39% and 31%, respectively. No treatment- or patient-specific variables were found to correlate with survival rates. Conclusions: In selected patients with liver metastases from breast cancer, an aggressive surgical approach is associated with favorable long-term survival. Hepatic resection should be considered a component of multimodality treatment of breast cancer in these patients.

Intraoperative ultrasound has become an essential tool for the surgeon in the field of hepatobiliary surgery. No preoperative study has been able to duplicate the sensitivity and specificity of IOUS in the identification of occult lesions. With recent improvements in technology, IOUS has now become an indispensable means of defining the extent of disease and respectability, and providing a guide to anatomic and nonanatomic hepatic resections and minimally invasive and percutaneous ablative techniques.

3603 Background: The two primary aims of NSABP R-04 were 1) Can the oral fluoropyrimidine, Cape be substituted for the standard of care in the curative setting of Stage II & III rectal cancer namely, CIV 5-FU, during neoadjuvant RT; and 2) Can the addition of Ox enhance the activity of fluoropyrimidine sensitized RT? Methods: Pts with clinical stage II or III rectal cancer undergoing preoperative RT (4,500cGy in 25 fractions over 5 wks + boost of 540cGy-1080cGy in 3-6 daily fractions) were randomly assigned to one of four chemotherapy regimens in a 2x2 design: CVI 5-FU (225mg/m2 5 days/wk), with or without intravenous Ox (50mg/m2 /wk x 5) or oral Cape (825 mg/m2 BID 5 days/wk), with or without Ox (50mg/m2/wk x 5). The primary endpoint was local-regional (L-R) tumor control that included L-R tumor recurrence, less than a complete surgical resection, and no surgery for any reason. Results: From July 2004 to August 2010, 1,608 patients were randomly assigned and 99.2% were eligible for analysis. There were n...

384 Background: Valentini, et al. (J Clin Oncol 29: 2011, 3163-72) developed nomograms for predicting overall survival (OS) based on clinical factors available after neoadjuvant therapy (tx). Pathologic T-stage (pT), N-stage (pN), and clinical T (cT) were the most important independent predictors of OS. We developed a neoadjuvant RC score (NAR score) using pN and downstaging of T (cT – pT) based on relative weights suggested by the nomograms. NSABP’s R-04 trial presents an opportunity for independent validation of the NAR score. Methods: Pts with clinical stage II/III RC undergoing preoperative RT (4,500cGy in 25 fractions over 5 wks + boost of 540-1,080cGy in 3-6 daily fractions) were randomized to one of four regimens in a 2x2 design: CVI 5-FU (225mg/m2 5 days/wk), with or without oxaliplatin (Ox) (50mg/m2 /wk x 5) or oral capecitabine (825 mg/m2 BID 5 days/wk), with or without Ox. The NAR score is computed as [5 pN – 3 (cT – pT) + 12]2/ 9.61 where: cT in {1, 2, 3, 4}, pT in {0, 1, 2, 3, 4}, and pN in {0, 1, 2}. The NAR score takes values from 0 to 100; higher scores indicate poorer prognosis. Analyses based on the score should be stratified by cT. NAR score is compared to pathologic complete response (ypCR) by Akaike’s information criterion (AIC) to determine the better predictor of OS. Results: 1,479 pts had data for the NAR score and follow-up for OS. Continuous NAR score was significantly associated with OS (HR/unit 1.04 95% CI 1.03-1.05, p

390 Background: The primary aims were to: 1) compare capecitabine (Cape) and continuous intravenous infusion (CVI) 5-FU combined with pelvic radiation therapy (RT) given preoperatively for patients (pts) with stage II or III rectal cancer; 2) determine whether the addition of oxaliplatin (Ox) would improve pt outcomes. Preliminary results focusing on pathologic complete response, sphincter-sparing surgery, surgical downstaging, and toxicity were presented at ASCO 2011 (Roh: J Clin Oncol 29: 2011 Ab 3503). Methods: Pts with clinical stage II or III rectal cancer undergoing preoperative RT (4,500cGy in 25 fractions over 5 wks + boost of 540cGy-1080cGy in 3-6 daily fractions) were randomly assigned to one of four chemotherapy regimens in a 2x2 design: CVI 5-FU (225mg/m2 5 days/wk), with or without intravenous Ox (50mg/m2 /wk x 5) or oral Cape (825 mg/m2 BID 5 days/wk), with or without Ox (50mg/m2/wk x 5). The primary endpoint of local-regional (L-R) tumor control included L-R tumor recurrence, less than an R0 resection (complete surgical resection), and no surgery. Results: From July 2004 to August 2010, 1608 patients were randomly assigned and 99.2% were eligible. There were no significant differences in L-R tumor control, DFS, or OS between regimens for either the 5-FU-Cape (L-R p=0.98) or the Ox-none (L-R p=0.70) comparisons. The addition of Ox was associated with significantly more grade 3-4 diarrhea (p80% of the ideal chemotherapy dose in combination with preoperative RT. Conclusions: CVI 5-FU or oral Cape combined with RT produced similar outcomes and toxicity profiles. Because use of oral Cape avoids the need for central venous catheters and ambulatory infusion pumps, it can be considered a new standard of care in this setting. The addition of Ox provided no improvement in outcomes but did add significant toxicity. Clinical trial information: NCT00058474.

Hepatocellular cancer (HCC) is one of the most commor cancers in the world and the incidence is increasing. There are regional differences in the incidence of the disease, with sub-Saharan Africa and the Far East with the highest incidence (>30/100,000) and Northern Europe and the United States with the lowest incidence (

This retrospective study was performed to assess the outcome among patients who underwent hepatic resection or tumor ablation after hepatic artery infusion (HAI) therapy down-staged previously unresectable hepatocellular carcinoma (HCC) or liver metastases from colorectal cancer (CRC).Between 1983 and 1998, 25 patients with HCC and 383 patients with hepatic CRC metastases were treated with HAI therapy for unresectable liver disease. We retrospectively reviewed the records of 26 (6%) of these patients who underwent subsequent surgical exploration for tumor resection or ablation.At a median of 9 months (range 7-12 months) after HAI treatment, four patients (16%) with HCC underwent exploratory surgery; two underwent resection with negative margins, and the other two were given radiofrequency ablation (RFA) because of underlying cirrhosis. At a median postoperative follow-up of 16 months (range 6-48 months), all four patients were alive with no evidence of disease. At a median of 14.5 months (range 8-24 months) after HAI therapy, 22 patients with hepatic CRC metastases underwent exploratory surgery; 10 underwent resection, 6 underwent resection and RFA or cryotherapy, and 2 underwent RFA only. At a median follow-up of 17 months, 15 (83%) of the 18 patients with CRC who had received surgical treatment had developed recurrent disease; the other 3 died of other causes (1 of postoperative complications) within 7 months of the surgery. One patient in whom disease recurred underwent a second resection and was disease-free at 1 year follow-up.Hepatic resection or ablation after tumor downstaging with HAI therapy is a viable option for patients with unresectable HCC. However, given the high rate of recurrence of metastases from CRC, hepatic resection or ablation after downstaging with HAI should be used with caution.

The majority of patients with primary or metastatic malignancies confined to the liver are not candidates for resection because of tumor size, location, multifocality, or inadequate functional hepatic reserve. Cryoablation has become a common treatment in select groups of these patients with unresectable liver tumors. However, hepatic cryoablation is associated with significant morbidity. Radiofrequency ablation (RFA) is a technique that destroys liver tumors in situ by localized application of heat to produce coagulative necrosis. In this study, we compared the complication and early local recurrence rates in patients with unresectable malignant liver tumors treated with either cryoablation or RFA.Patients with hepatic malignancies were entered into two consecutive prospective, nonrandomized trials. The liver tumors were treated intraoperatively with cryoablation or RFA; intraoperative ultrasonography was used to guide placement of cryoprobes or RFA needles. All patients were followed up postoperatively to assess complications, treatment response, and local recurrence of malignant disease.Cryoablation was performed on 88 tumors in 54 patients, and RFA was used to treat 138 tumors in 92 patients. Treatment-related complications, including 1 postoperative death, occurred in 22 of the 54 patients treated with cryoablation (40.7% complication rate). In contrast, there were no treatment-related deaths and only 3 complications after RFA (3.3% complication rate, P0.001). With a median follow-up of 15 months in both patient groups, tumor has recurred in 3 of 138 lesions treated with RFA (2.2%), versus 12 of 88 tumors treated with cryoablation (13.6%, P0.01).RFA is a safe, well-tolerated treatment for patients with unresectable hepatic malignancies. This study indicates that (1) complications occur much less frequently following RFA of liver tumors compared with cryoablation of liver tumors, and (2) early local tumor recurrence is infrequent following RFA.

The case described here illustrates the antitumor activity of a four-drug systemic combination chemobiotherapy with platinol, recombinant interferon alpha 2b, doxorubicin (Adriamycin), and 5-fluorouracil (5-FU) (PIAF) in a patient with diffuse hepatocellular carcinoma involving the liver and lungs.

It was estimated that there would be 131,200 new cases of colon and rectal cancer in 1997 in the United States and 54,900 deaths due to colon and rectal cancer.1 Ninety percent of patients who die from colorectal cancer have liver metastases.2 The liver is the most prevalent site of first or only recurrence.3 Liver metastases occur in 40–75% of patients with colorectal cancer, but only 10–30% have metastatic disease limited to the liver.4,5 Surgical resection of hepatic metastases remains the treatment of choice when feasible, but only 5–10% of patients are considered candidates for liver resection.6,7 Patients with limited liver metastases from colorectal cancer who do not undergo hepatic resection rarely survive more than 2 years after diagnosis.8,9 Five-year survival rates of 25–35% have been reported in patients who have undergone hepatic resection of colorectal metastases.10,11 Unfortunately, at least 75% of patients with limited liver-only metastases are not candidates for surgical resection.12 Patients who have multiple metastases involving both the right and left lobes of the liver, metastatic lesions in proximity to major blood vessels or biliary structures where a 1-cm margin of clearance cannot be achieved, or more than three or four liver metastases have usually been considered to have unresectable lesions and do not qualify for standard hepatic surgical resection.8,10,13,14

Although a variety of new treatment modalities for hepatocellular carcinoma (HCC) have been explored in the past few years, the fact remains that surgical resection provides the only chance for long-term survival in this aggressive disease. Five-year survival rates after curative surgery average 18-36%. In general, a resectable tumor must be (1) confined to the liver (absence of vascular invasion or distant metastases) and (2) entirely encompassed by local excision with an adequate margin. In order to be a candidate for resection, the patient must also have adequate liver reserve. Only 10-15% of patients with primary liver cancer meet these requirements. Unfortunately, the majority of these patients develop recurrence and do not benefit from further resection.

Staging systems aim to stratify patients into groups with similar prognoses. As such, these staging systems may serve to guide choice of therapy, aid in patient counseling, allow comparisons of the end results of therapy, and facilitate patient selection and randomization for research protocols.

Hepatic arterial infusion (HAI) of floxuridine is often used for metastatic colorectal cancer, though this is associated with dose-limiting hepatobiliary toxicity. A phase I trial was initiated to determine if circadian-patterned HAI floxuridine would reduce toxicity. Twenty-one patients were enrolled, and they received a continuous 14-day HAI of floxuridine, with 90-95% of the drug delivered over the same six-hour period daily. The therapy was tolerable, but there was no reduction in hepatobiliary toxicity. The response rate of 33% (1 complete and 6 partial responses) was similar to that of regimens that do not utilize circadian timing. HAI floxuridine chronotherapy for metastatic colorectal cancer cannot be recommended.

Hepatic resection remains the only chance for cure in patients with colorectal liver metastases. The challenge remains in preoperatively identifying the patient who will benefit from resective therapy. Numerous contraindications to hepatic resection for colorectal liver metastases have been identified, but one consistent and discriminatory factor has been the presence of extrahepatic disease. The significance of disease beyond the liver is based on no 5-year survivors in whom a simultaneous resection of extrahepatic disease and hepatectomy had been performed. 1 The dogma was that the presence of metastatic disease in the liver and other location(s) indicated a disseminated systemic phenomena and was beyond the ability of surgical resection to completely extirpate the disease. Multiple macroscopic sites predicted that microscopic metastases were also present and would eventually become clinically evident and ultimately lead to the demise of the patient. The patient was guaranteed to experience recurrent disease that would preclude cure. This dictum may no longer be correct and has been effectively challenged. In this issue of the Annals of Surgical Oncology , Elias et al. 2 have shown that resecting extrahepatic disease and performing a hepatectomy can provide long-term survival in patients with advanced disease. The authors have shown that not all patients with extrahepatic disease automatically harbor microscopic metastases that prevent a curative hepatic resection. Over a 14-year period 75 patients underwent a complete R0 resection of extrahepatic disease simultaneously with hepatectomy. The overall 5-year survival was 28% as compared with 33% in the 219 patients undergoing hepatic resection without extrahepatic disease at the same institution during the same time period. These results will require confirmation by other liver surgeons. In patients that underwent a R1-2 resection, 5-year survival was 7%. Although a distinctly worse outcome, it is superior to patients that did not undergo a hepatic resection. Forty-three patients were considered unresectable (secondary to number or location of hepatic metastases) at the time of presentation and underwent neoadjuvant systemic chemotherapy (5-fluorouracil/leukovorin, plus oxaliplatin or irinotecan). Every patient had an objective response to preoperative therapy and became eligible for hepatectomy. The survival in this group remained inferior to the group of patients that were initially resectable at presentation (13% vs. 41%), which reflects more aggressive disease. Nevertheless, converting every patient with unresectable disease to resectable is remarkable. This observation suggests that the administration of neoadjuvant systemic chemotherapy should be offered to all patients with colorectal liver metastases and may improve overall survival. Not all of the patients will derive benefit from simultaneous resections. Several significant prognostic factors were identified in multivariate analysis. Patients with more than five metastases and multiple sites of extrahepatic disease had a significantly worse survival. The site of extrahepatic disease, pre- or intraoperative discovery of the extrahepatic disease, and repeat hepatectomy were not significant factors in predicting outcome. This article is a significant step in expanding the indications for hepatic resection. This work has shown that in select patients, the presence of extrahepatic disease is no longer a distinct contraindication to performing hepatic resection. Simultaneous resection of extrahepatic disease and hepatectomy should be considered in patients with 1) less than five hepatic metastases that can be resected with a tumor-free margin and 2) a single site of extrahepatic disease that can be resected with a tumor-free margin. To provide benefit, all patients must undergo an R0 resection.

Bilateral gracilis myocutaneous flaps were originally used as part of a technique for creating a neovagina following total pelvic exenteration. Based upon this experience, we began using single flaps for primary repair and closure of large surgical defects in the perineal area that require alternate tissue sources to replace lost skin, mucosa, or adjacent deep tissues. Eighteen single gracilis flaps were used for major vulvovaginal reconstructions in 17 women during the past 5 years. Women undergoing unilateral flap reconstructions included 6 with anorectal cancers and 11 with vulvovaginal tumors. Most patients were being treated for recurrence after failed primary therapy (n = 7) or were receiving multimodal treatment for advanced local disease (n = 7). All cases involved complex resections followed by simultaneous reconstruction: mean total operative time was 377 min with a mean estimated blood loss of 1010 cc. Reconstruction involved external flap placement on the vulva or perineum in 7 cases and internal placement to replace excised portions of the vagina in the other 11. Mean flap size was 6.6 x 11.4 cm. Necrosis of flap skin occurred in 3 patients; minor wound separations or flap edge necrosis was seen in 5 cases. Hospital stay averaged 18.4 days. Nine women had recurrent disease and died over 4-30 months; the remaining 8 are alive and disease free with a median follow-up of 25 months. The single gracilis flap provides a versatile method for providing anatomic reconstruction of large perineal defects in women who have undergone extensive resection.

PURPOSE To conduct a pilot trial of hepatic arterial infusion (HAI) of floxuridine (FUDR), leucovorin, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (FLAP) in nonresectable hepatocellular cancer (HCC) confined to the liver and assess the effects of hepatitis B (HBV) and hepatitis C (HCV) viral markers on toxicity, response to treatment, and patient survival. PATIENTS AND METHODS Of 31 HCC patients, 13 were HBV- and HCV-nonreactive, and 18 had evidence of either current or prior HBV and/or HCV infection. Treatment was delivered through percutaneous hepatic arterial catheters, and Infusaid pumps (Shiley Infusaid, Norwood, MA) were placed in responding patients. Cisplatin (100 mg/m2) and Adriamycin (30 to 35 mg/m2) were administered on day 1, followed by a continuous 24-hour HAI of an admixture of floxuridine (60 mg/m2) and leucovorin (15 mg/m2) daily for 4 days. Treatment was repeated every 5 weeks. RESULTS Twelve (41%) of 29 assessable patients had a partial response (PR), with a median time to disease progression of 13 months. Six (50%) of 12 HBV-negative (HBV-)/HCV-negative (HCV-) and six of 17 (35%) HBV-positive (HCV+) and/or HCV-positive (HCV+) patients achieved a PR. Eight patients have been maintained in remission for a median duration greater than 15.5 months. The median survival duration of all 31 patients was 15 months, 7.5 months among HBV+ and/or HCV+ patients, and significantly longer among hepatitis-non-reactive patients (P = .007). (A median has not yet been reached.) Granulocylopenia (< 0.1 x 10(3)/microL), thrombocytopenia (< 25 x 10(3)/microL), and hospitalizations for infectious complications were significantly more common among HBV-HCV-reactive than -nonreactive patients: 56%, 50%, and 67% versus 15%, 15%, and 8%, respectively (P < .05 for all). CONCLUSION HAI of FLAP has induced long-term PR and has palliated extensive nonresectable HCC. Positive hepatitis serology appeared to increase bone marrow susceptibility to myelotoxic drugs. Conceivably, one or both viruses may have a direct inhibitory effect on bone marrow progenitors and thereby contribute to the observed myelotoxicity.

Hepatocellular carcinoma (HCC) remains one of the world’s most common deadly cancers. During the past several years progress in the treatment of this malignancy has been slow despite numerous advances in imaging, resection techniques, transplantation, perioperative care, and palliative options. Unfortunately, most patients who present with HCC are unresectable at the time of their diagnosis and are therefore not curable. For these patients a variety of palliative treatment modalities exist, some of which are effective in enhancing the quality of life and prolonging survival. For the potentially resectable patient, a number of factors must be considered before resection is performed. Determining resectability in patients with HCC can be difficult. They represent a more challenging group than some other patients with liver tumors, such as those with colorectal hepatic metastases, in that many HCC patients with resectable tumors carry the added burden of cirrhosis and/or chronic hepatitis. This adds the another dimension to the preoperative workup, which determines whether a technically resectable patient will have sufficient hepatic reserve to survive the postoperative stress of hepatic resection. The majority of operative mortality from liver resection for HCC is caused by hepatic failure. In this chapter we focus upon the current staging workup for the potentially resectable patient, operative decisionmaking and techniques, and the factors dictating prognosis for the resected patient.

3503 Background: The optimal chemotherapy regimen to be given concurrently with preop radiation therapy (RT) in patients with resectable adenocarcinoma of the rectum is unknown. NSABP R-04 compared the efficacy of 4 chemotherapy regimens administered concomitantly with preop RT. Methods: Patients with clinical stage II or III rectal cancer undergoing preop RT (4,500cGy in 25 fractions over 5 wk + boost of 540cGy-1080cGy in 3-6 daily fractions) were randomly assigned to one of the following chemotherapy regimens: continuous IV infusion (CVI) 5-FU (225mg/m2 5 days/wk), with or without IV oxaliplatin (OX) (50mg/m2 /wk x 5); oral capecitabine (CAPE) (825 mg/m2 BID 5 days/wk), with or without OX (50mg/m2/wk x 5). Prior to random assignment the surgeon indicated if the patient was eligible for sphincter-saving surgery (SSS) based on clinical staging. The endpoints were complete pathologic response (pCR), SSS, and surgical downstaging (SD, conversion to SSS). Results: From July 2004 to August 2010, 1,608 patient...