Showing papers in "Annals of Surgical Oncology in 2009"

Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement.

Abstract: Preoperative Staging and Defining Resectability From a surgical perspective, the first objective in the management of suspected or confirmed pancreatic cancer is to determine the potential for resection. Routine exploratory laparotomy for the purpose of operatively determining resectability has been diminished by modern 3-D radiographic imaging, along with effective and sustainable nonoperative methods of palliation. Careful correlation between preoperative CT findings and surgical results has better-defined CT criteria for resectability. The critical aspects that need be evaluated in a thorough radiographic assessment are the presence or absence of peritoneal or hepatic metastases; the potential involvement of the SMV and portal vein and the relationship of these vessels and their tributaries to the tumor; the relationship of the tumor to the SMA, celiac axis, hepatic artery, and gastroduodenal artery; and the presence of any aberrant vascular anatomy. Unequivocal radiographic findings contraindicating resection include distant metastases, major venous thrombosis of the portal vein or SMV extending for several centimeters, and circumferential encasement of the SMA, celiac axis or proximal hepatic artery. Recent revisions of the National Comprehensive Cancer Network (NCCN) guidelines were an attempt to distinguish locally advanced unresectable tumors from potentially resectable tumors.22 Ambiguity exists in these guidelines because of the lack of clarity in defining clearly resectable situations from “borderline resectable” tumors and because of the subjective criteria used to define “borderline” tumors relative to locally advanced, unresectable lesions. The NCCN guidelines do offer a definition of what should be considered a radiographically resectable tumor. Patients without distant metastases and no evidence of tumor extension to the SMV and portal vein and clear fat planes around the celiac axis, the hepatic artery, and SMA should be categorized as having localized and resectable cancers. More refined and objective criteria have been proposed by the M. D. Anderson Cancer Center Pancreas Cancer Group in an attempt to better define the term “borderline resectable” and to guide treatment decisions regarding the use of neoadjuvant therapy and the high likelihood of vein resection and reconstruction as a means to improve the rate of a complete and margin-negative resection.23 Radiographic findings of tumor abutment on the portal vein or SMV with or without venous deformity, and limited encasement of the mesenteric vein and portal vein (i.e., short segment occlusion with suitable vessel for anastomosis above and below) represent the extent of venous involvement that would categorize a tumor as borderline resectable. Radiographic findings suggesting borderline arterial involvement as defined by M. D. Anderson Cancer Center include encasement of a short segment of the hepatic artery, without evidence of tumor extension to the celiac axis and/or tumor abutment of the SMA involving < 180° of the artery circumference. In patients without clinically important major comorbidities, and in the absence of radiographic findings to suggest metastatic disease or locally advanced unresectable disease as outlined above, surgical resection should be considered feasible and likely to be achievable. Whether these resections would result in a higher-than-expected rate of margin-positive resections, and whether such resections would affect survival would best be determined by careful examination of outcomes relative to extent of vascular involvement using objective criteria to determine categorization of extent of disease. Consensus Statement 1. Tumors considered localized and resectable should demonstrate the following: a. No distant metastases. b. No radiographic evidence of SMV and portal vein abutment, distortion, tumor thrombus, or venous encasement. c. Clear fat planes around the celiac axis, hepatic artery, and SMA. 2. Tumors considered borderline resectable include the following: a. No distant metastases. b. Venous involvement of the SMV/portal vein demonstrating tumor abutment with or without impingement and narrowing of the lumen, encasement of the SMV/portal vein but without encasement of the nearby arteries, or short segment venous occlusion resulting from either tumor thrombus or encasement but with suitable vessel proximal and distal to the area of vessel involvement, allowing for safe resection and reconstruction. c. Gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct abutment of the hepatic artery, without extension to the celiac axis. d. Tumor abutment of the SMA not to exceed >180° of the circumference of the vessel wall.

The FLARE™ Intraoperative Near-Infrared Fluorescence Imaging System: A First-in-Human Clinical Trial in Breast Cancer Sentinel Lymph Node Mapping

Abstract: Background Invisible NIR fluorescent light can provide high sensitivity, high-resolution, and real-time image-guidance during oncologic surgery, but imaging systems that are presently available do not display this invisible light in the context of surgical anatomy. The FLARE™ imaging system overcomes this major obstacle.

Long-Term Survival After Multidisciplinary Management of Resected Pancreatic Adenocarcinoma

Abstract: Introduction Actual 5-year survival rates of 10–18% have been reported for patients with resected pancreatic adenocarcinoma (PC), but the use of multimodality therapy was uncommon in these series. We evaluated long-term survival and patterns of recurrence in patients treated for PC with contemporary staging and multimodality therapy.

Robotic versus laparoscopic low anterior resection of rectal cancer: short-term outcome of a prospective comparative study.

Abstract: Background The aim of this study is to compare the short-term results between robotic-assisted low anterior resection (R-LAR), using the da Vinci® Surgical System, and standard laparoscopic low anterior resection (L-LAR) in rectal cancer patients.

Desmoid-Type Fibromatosis: A Front-Line Conservative Approach to Select Patients for Surgical Treatment

Abstract: Purpose Surgery is still the standard treatment for desmoid-type fibromatosis (DF). Recently, the Institut Gustave Roussy (IGR), Villejuif, France, reported a series of patients treated with a front-line conservative approach (no surgery and no radiotherapy). The disease remained stable in more than half of patients. This study was designed to evaluate this approach on the natural history of the disease in a larger series of patients.

The risk of developing arm lymphedema among breast cancer survivors: a meta-analysis of treatment factors.

Abstract: As more women survive breast cancer, long-term complications that affect quality of life, such as lymphedema of the arm, gain greater importance. Numerous studies have attempted to identify treatment and prognostic factors for arm lymphedema, yet the magnitude of these associations remains inconsistent. A PubMed search was conducted through January 2008 to locate articles on lymphedema and treatment factors after breast cancer diagnosis. Random-effect models were used to estimate the pooled risk ratio. The authors identified 98 independent studies that reported at least one risk factor of interest. The risk ratio (RR) of arm lymphedema was increased after mastectomy when compared with lumpectomy [RR = 1.42; 95% confidence interval (CI) 1.15–1.76], axillary dissection compared with no axillary dissection (RR = 3.47; 95% CI 2.34–5.15), axillary dissection compared with sentinel node biopsy (RR = 3.07; 95% CI 2.20–4.29), radiation therapy (RR = 1.92; 95% CI 1.61–2.28), and positive axillary nodes (RR = 1.54; 95% CI 1.32–1.80). These associations held when studies using self-reported lymphedema were excluded. Mastectomy, extent of axillary dissection, radiation therapy, and presence of positive nodes increased risk of developing arm lymphedema after breast cancer. These factors likely reflected lymph node removal, which most surgeons consider to be the largest risk factor for lymphedema. Future studies should consider examining sentinel node biopsy versus no dissection with a long follow-up time post surgery to see if there is a benefit of decreased lymphedema compared with no dissection.

Obtaining adequate surgical margins in breast-conserving therapy for patients with early-stage breast cancer: current modalities and future directions.

Abstract: Inadequate surgical margins represent a high risk for adverse clinical outcome in breast-conserving therapy (BCT) for early-stage breast cancer. The majority of studies report positive resection margins in 20% to 40% of the patients who underwent BCT. This may result in an increased local recurrence (LR) rate or additional surgery and, consequently, adverse affects on cosmesis, psychological distress, and health costs. In the literature, various risk factors are reported to be associated with positive margin status after lumpectomy, which may allow the surgeon to distinguish those patients with a higher a priori risk for re-excision. However, most risk factors are related to tumor biology and patient characteristics, which cannot be modified as such. Therefore, efforts to reduce the number of positive margins should focus on optimizing the surgical procedure itself, because the surgeon lacks real-time intraoperative information on the presence of positive resection margins during breast-conserving surgery. This review presents the status of pre- and intraoperative modalities currently used in BCT. Furthermore, innovative intraoperative approaches, such as positron emission tomography, radioguided occult lesion localization, and near-infrared fluorescence optical imaging, are addressed, which have to prove their potential value in improving surgical outcome and reducing the need for re-excision in BCT.

Blood Neutrophil-to-Lymphocyte Ratio Predicts Survival in Patients with Colorectal Liver Metastases Treated with Systemic Chemotherapy

Abstract: Background Whether neutrophil-to-lymphocyte ratio (NLR) predicts survival of patients with colorectal liver metastases (CLM) treated with systemic chemotherapy remains unclear.

Are Mastectomies on the Rise? A 13-Year Trend Analysis of the Selection of Mastectomy Versus Breast Conservation Therapy in 5865 Patients

Abstract: The equivalency of survival between mastectomy and breast conservation therapy (BCT) has long been established, resulting in two decades of predominant BCT. Recently, surgeons have recognized a trend toward increasing mastectomy. Institutional trends of mastectomy and BCT were reviewed, confirming this perception in the surgical treatment of breast cancer. This report evaluates the factors that influence patient decisions to choose surgical therapies. Patients who underwent mastectomy or BCT for invasive and in situ breast cancer were identified upon retrospective review of a prospectively accrued breast cancer database between 1994 and 2007. Univariate and multivariate logistic regression analysis were used to estimate the odds ratio (OR) of the association between mastectomy and patients’ clinicopathologic characteristics. Of the 5,865 patients, 3,736 underwent BCT and 2,129 underwent mastectomy. The overall surgical volume decreased during the study period. Mastectomy rates during the periods of 1994–1998, 1999–2003, and 2004–2007 were 33%, 33%, and 44%, respectively (P < 0.01). Immediate reconstruction rates decreased during the same time periods from 16%, 5%, and 7%, respectively (P < 0.01). On logistic regression analysis, gender, age < 40 years, increase tumor size, and lymphovascular invasion were significant independent predictors of mastectomy. The mastectomy rate increased during the period 1999–2003 (OR 1.2) and during 2004–2007(OR 1.8). The perception of an increasing choice toward mastectomy has been confirmed at this institution. Possible reasons are younger population with higher lifetime risk, higher stage disease, and more biologically aggressive or diffuse tumors. Patient preference, fear of genetic or recurrence risk, and “intangible” factors seem to shift decisions toward mastectomy.

Correlation of CD133, OCT4, and SOX2 in rectal cancer and their association with distant recurrence after chemoradiotherapy.

Abstract: Background Cancer stem cells are associated with metastatic potential, treatment resistance, and poor patient prognosis. Distant recurrence remains the major cause of mortality in rectal cancer patients with preoperative chemoradiotherapy (CRT). We investigated the role of three stem cell markers (CD133, OCT4, and SOX2) in rectal cancer and evaluated the association between these gene levels and clinical outcome in rectal cancer patients with preoperative CRT.

Pain Palliation in Patients with Bone Metastases Using MR-Guided Focused Ultrasound Surgery: A Multicenter Study

Abstract: Noninvasive thermal ablation using magnetic resonance (MR)-guided focused ultrasound (MRgFUS) has been shown to be clinically effective in uterine fibroids, and is being evaluated for ablation of breast, liver, and brain lesions. Recently MRgFUS has been evaluated for palliation of pain caused by bone metastases. We present the clinical results of a multicenter study using MRgFUS for palliation of bone metastases pain. A multicenter study to evaluate the safety and efficacy of MRgFUS palliative treatment of bone metastases was conducted in patients suffering from painful metastatic bone lesions for which other treatments were either ineffective or not feasible. Thirty-one patients with painful bone metastases underwent the MRgFUS procedure in three medical centers. Treatment safety was evaluated by assessing the device-related complications. Effectiveness of pain palliation was evaluated using the visual analog pain score (VAS), and measurable changes in the intake of opioid analgesics. Thirty-six procedures were performed on 31 patients. Mean follow-up time was 4 months. 25 patients underwent the planned treatment and were available for 3 months post-treatment follow-up. 72% of the patients (18/25) reported significant pain improvement. Average VAS score was reduced from 5.9 prior to treatment to 1.8 at 3 months post treatment. 67% of patients with recorded medication data reported a reduction in their opioid usage. No device-related severe adverse events were recorded. The results suggest that MRgFUS has the ability to provide an accurate, effective, and safe noninvasive palliative treatment for patients with bone metastases.

Bleomycin-Based Electrochemotherapy: Clinical Outcome from a Single Institution’s Experience with 52 Patients

Abstract: Electrochemotherapy (ECT) has emerged as a complementary treatment for superficial metastases. Fifty-two consecutive patients with different cancer histotypes, mainly melanoma and breast cancer, with disease unsuitable for conventional treatments underwent bleomycin-based ECT for cutaneous and subcutaneous metastases. Toxicity, local response, response duration, and the impact on quality of life were evaluated. A total of 608 tumor nodules were treated (mean, 12 per patient), with 27% of patients affected by nodules >3 cm in size. Treatment was tolerated well, especially under general sedation. An objective response was obtained in 50 (96%) of 52 patients 1 month after the first application. Twenty-two patients underwent a second treatment (because of partial response or the appearance of new lesions). Partial response at first ECT achieved a response consolidation at second application: 80% complete response, 20% partial response. Some patients underwent up to five treatments because of new lesions, but maintained superficial tumor control. After a mean follow-up of 9 (range, 2-21) months, only two patients experienced relapse in the treatment field. Through a nonvalidated eight-item questionnaire (assessing wound healing and bleeding, aesthetic impairment, daily activities, social relations, pain, treatment satisfaction, acceptance of retreatment), most patients reported a benefit in local disease-related complaints and in activity of daily living. In a palliative setting, ECT proved to be safe, effective in all tumors treated, and useful in preserving patients' quality of life. This benefit, although preliminary, deserves further assessment after a formal validation of the dedicated questionnaire.

Inhibition of Autophagy by 3-MA Enhances the Effect of 5-FU-Induced Apoptosis in Colon Cancer Cells

Abstract: Background 5-fluorouracil-(5-FU)-based adjuvant chemotherapy is widely used for the treatment of colorectal cancer. However, 5-FU resistance in the course of treatment has become more common. Therefore, new therapeutic strategies and/or new adjuvant drugs still need to be explored.

Evaluation of preoperative computed tomography in estimating peritoneal cancer index in colorectal peritoneal carcinomatosis.

Abstract: Peritoneal Cancer Index (PCI) has been recognized as an independent prognostic indicator for long-term outcomes. It also influences the likelihood of complete cytoreduction, another principal determinant of long-term survival. The objective of this study was to evaluate the utility of preoperative CT in estimating PCI during the patient selection process. The efficacy of CT in demonstrating peritoneal disease was evaluated by comparing the radiological and intraoperative lesion size and PCI scores using the Wilcoxon signed-rank test. Tumor distribution was assessed in each abdominopelvic region as tumor present versus absent. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated in each abdominopelvic region. Overall, where CT identifies the presence of disease, it portrayed lesion size accurately in 60%, underestimated in 33%, and overestimated in 7% of cases. Analysis of individual abdominopelvic regions demonstrated a statistically significant difference between radiologically and intraoperatively visualized lesion sizes (P < 0.05) except in the epigastrium, left upper, and left flank regions. The sensitivity of CT in detecting peritoneal implants was influenced by lesion size. Small nodules (<0.5 cm) were visualized on CT with only a sensitivity of 11%, which is in contrast to 94% with nodules exceeding 5 cm. Radiological PCI scores significantly underestimated intraoperative PCI (P < 0.001). This study demonstrated that the sensitivity of CT in detecting peritoneal implants was influenced by lesion size and CT PCI significantly underestimated clinical PCI. The role of CT in refining patient selection and improving prognosis remains to be closely evaluated.

The Prognosis and Survival Outcome of Intrahepatic Cholangiocarcinoma Following Surgical Resection: Association of Lymph Node Metastasis and Lymph Node Dissection with Survival

Abstract: Surgical resection has been shown to improve long-term survival for patients with intrahepatic cholangiocarcinoma (ICC). The benefit of lymph node dissection is still controversial. The aims of this study were to investigate the prognostic factors of ICC and to examine the impact of lymph node metastasis and extent of lymph node dissection on survival. A total of 64 patients with ICC were operated on with curative intent and resultant macroscopic curative resection (R0 and R1). The patients were classified according to the extent of the lymph node dissection. Clinicopathological characteristics and survival were reviewed retrospectively. All patients underwent anatomical resection. The 5-year survival rates were 39.5%. Multivariate analysis revealed that lymph node metastasis (hazard ratio: 3.317) was an independent prognostic factors on survival. Recurrence occurred in 41 patients. Median disease-free survival time was 12.3 months. Tumor differentiation was an independent prognostic factor for disease-free survival (hazard ratio: 3.158). The extent of lymph node dissection did not affect the occurrence of complication. Regional + α lymph node dissection group demonstrated similar survival to those of lymph node sampling group, although significant high incidence of lymph node metastases was observed in the regional + α lymph node dissection group. The extent of lymph node dissection did not affect the survival in the patients without lymph node involvement. The regional + α lymph node dissection enhanced the survival in the ICC patients with lymph node metastasis, and the exact nodal status could be confirmed by lymph node dissection in the pericholedochal lymph nodes.

A Proposed Staging System for Intrahepatic Cholangiocarcinoma

Abstract: The American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) staging system for liver cancer is based on data exclusively derived from hepatocellular carcinoma (HCC) patients and thus may be inappropriate for patients with intrahepatic cholangiocarcinoma (ICC). We sought to empirically derive an ICC staging system from population-based data on patients with ICC. The Surveillance, Epidemiology, and End Results (SEER) database was used to identify 598 patients who underwent surgery for ICC between 1988 and 2004. The discriminative abilities of the AJCC/UICC liver cancer and two Japanese ICC staging systems were evaluated. Independent predictors of survival were identified using Cox proportional hazards models. A staging system for ICC was then derived based on these analyses. The AJCC/UICC T classification system failed to adequately stratify the T2 and T3 cohorts due to tumor size >5 cm not being a relevant prognostic factor [hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.72-1.30]. In contrast, presence of multiple lesions (HR 1.42, 95% CI 1.01-2.01) or vascular invasion (HR 1.53, 95% CI 1.10-2.12) predicted adverse prognosis. Based on these findings, an ICC staging system was developed that omits tumor size. This system showed no loss of prognostic discrimination compared with the AJCC/UICC system and significant superiority over the Japanese systems. We conclude that the AJCC/UICC liver cancer staging system fails to stratify ICC patients adequately and inappropriately includes tumor size. We propose a staging system specifically developed for ICC based on number of tumors, vascular invasion, lymph node status, and presence of metastatic disease.

Combined modality treatment of resectable and borderline resectable pancreas cancer: expert consensus statement.

Abstract: Department of Radiation Oncology, Rush University Medical Center, Chicago, IL; Division of Surgical Oncology, University of California at San Diego, San Diego, CA; Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York; Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX; Pancreaticobiliary Cancer, Digestive Diseases Institute, Virginia Mason Medical Center, Seattle, WA; Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX

A Systematic Review and Meta-Analysis of Cytoreductive Surgery with Perioperative Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis of Colorectal Origin

Abstract: Background The objective of the present meta-analysis was to analyze the survival outcomes of patients with colorectal peritoneal carcinomatosis (CRPC), with particular focus on cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC).

How good is endoscopic ultrasound in differentiating various T stages of rectal cancer? Meta-analysis and systematic review.

Abstract: Published data on accuracy of endoscopic ultrasound (EUS) in differentiating T stages of rectal cancers is varied. Study selection criteria were to select only EUS studies confirmed with results of surgical pathology. Articles were searched in Medline and Pubmed. Pooling was conducted by both fixed and random effects models. Initial search identified 3,630 reference articles, of which 42 studies (N = 5,039) met the inclusion criteria and were included in this analysis. The pooled sensitivity and specificity of EUS to determine T1 stage was 87.8% [95% confidence interval (CI) 85.3–90.0%] and 98.3% (95% CI 97.8–98.7%), respectively. For T2 stage, EUS had a pooled sensitivity and specificity of 80.5% (95% CI 77.9–82.9%) and 95.6% (95% CI 94.9–96.3%), respectively. To stage T3 stage, EUS had a pooled sensitivity and specificity of 96.4% (95% CI 95.4–97.2%) and 90.6% (95% CI 89.5–91.7%), respectively. In determining the T4 stage, EUS had a pooled sensitivity of 95.4% (95% CI 92.4–97.5%) and specificity of 98.3% (95% CI 97.8–98.7%). The p value for chi-squared heterogeneity for all the pooled accuracy estimates was > 0.10. We conclude that, as a result of the demonstrated sensitivity and specificity, EUS should be the investigation of choice to T stage rectal cancers. The sensitivity of EUS is higher for advanced disease than for early disease. EUS should be strongly considered for T staging of rectal cancers.

Sentinel-lymph-node-based management or routine axillary clearance? One-year outcomes of sentinel node biopsy versus axillary clearance (SNAC): a randomized controlled surgical trial.

Abstract: We sought the extent to which arm morbidity could be reduced by using sentinel-lymph-node-based management in women with clinically node-negative early breast cancer. One thousand eighty-eight women were randomly allocated to sentinel-lymph-node biopsy followed by axillary clearance if the sentinel node was positive or not detected (SNBM) or routine axillary clearance (RAC, sentinel-lymph-node biopsy followed immediately by axillary clearance). Sentinel nodes were located using blue dye, alone or with technetium-labeled antimony sulfide colloid. The primary endpoint was increase in arm volume from baseline to the average of measurements at 6 and 12 months. Secondary endpoints were the proportions of women with at least 15% increase in arm volume or early axillary morbidity, and average scores for arm symptoms, dysfunctions, and disabilities assessed at 6 and 12 months by patients with the SNAC Study-Specific Scales and other quality-of-life instruments. Sensitivity, false-negative rates, and negative predictive values for sentinel-lymph-node biopsy were estimated in the RAC group. The average increase in arm volume was 2.8% in the SNBM group and 4.2% in the RAC group (P = 0.002). Patients in the SNBM group gave lower ratings for arm swelling (P < 0.001), symptoms (P < 0.001), and dysfunctions (P = 0.02), but not disabilities (P = 0.5). Sentinel nodes were found in 95% of the SNBM group (29% positive) and 93% of the RAC group (25% positive). SNB had sensitivity 94.5%, false-negative rate 5.5%, and negative predictive value 98%. SNBM was successfully undertaken in a wide range of surgical centers and caused significantly less morbidity than RAC.

Patient and Surgeon Characteristics Associated with Increased Use of Contralateral Prophylactic Mastectomy in Patients with Breast Cancer

Abstract: Patients with unilateral breast cancer have an increased risk of developing contralateral breast cancer. A recent population-based study demonstrated that the proportion of patients with unilateral breast cancer in the United States who underwent contralateral prophylactic mastectomy (CPM) has increased by 150% in recent years. The current study evaluated patients who underwent breast cancer surgery in a metropolitan-based hospital system to determine factors associated with CPM. We reviewed the records of all patients who underwent surgical treatment for breast cancer in 2006 and 2007 in a single health care system, which included six different hospitals. Exclusion criteria included preoperative diagnosis of bilateral disease, stage IV disease, and a history of previous breast cancer. We recorded patient, treatment, tumor, and surgeon characteristics. Multivariate logistic regression models were used to predict CPM use. Of 571 eligible patients, 276 (48.3%) underwent breast-conserving surgery (BCS), 130 (22.8%) underwent unilateral mastectomy, and 165 (28.9%) underwent mastectomy and a CPM. Among mastectomy patients, 55.9% underwent CPM. Young age ( 55 years), large tumor size (>5 vs. <2 cm), positive family history, lobular histology, multicentric disease, and surgeon gender (female) were independent predictors of increased CPM rates. Body mass index, tumor grade, estrogen receptor status, and preoperative breast magnetic resonance imaging were not associated with increased CPM rates. Our study is the first to evaluate specific surgeon characteristics associated with CPM use. Prospective studies are needed to examine factors affecting patient decision-making to develop resources that may assist patients in this process.

Analysis of the Extent of Resection for Adenocarcinoma of the Gallbladder

Abstract: Gallbladder cancer has historically been considered an incurable malignancy; although, extended resection has been associated with cure in selected patients. However, the optimal extent of resection is unknown. The objective of this study was to analyze the impact of the extent of resection for gallbladder adenocarcinoma on disease-specific survival (DSS) and perioperative morbidity. Analysis of a prospective hepatobiliary surgery database identified patients undergoing surgical resection for gallbladder adenocarcinoma from 1990 to 2002. Clinicopathologic factors including extent of resection were analyzed for their association with DSS and perioperative morbidity. Long-term outcome was evaluable in 104 patients. With median follow-up of 58 months for survivors, the actuarial 5-year DSS was 42%. Thirty-six patients (35%) underwent major hepatectomy, but in 15 this was not mandatory to clear all disease. Sixty-eight patients (65%) underwent common bile duct (CBD) excision, but 32 were performed empirically. Twenty-one patients (20%) underwent en bloc resection of adjacent organs other than the liver. The performance of a major hepatectomy or a CBD excision was not associated with other clinicopathologic variables or long-term survival. Resection of adjacent organs were associated with advanced T stage but not with survival. T stage, N stage, histologic differentiation, and CBD involvement were independently associated with survival. Major hepatectomy and CBD excision were significantly associated with perioperative morbidity. We conclude that tumor biology and stage, rather than extent of resection, predict outcome after resection for gallbladder cancer. Major hepatic resections, including major hepatectomy and CBD excision, are appropriate when necessary to clear disease but are not mandatory in all cases.

Liver cell adenoma: A multicenter analysis of risk factors for rupture and malignancy

Abstract: Liver cell adenoma (LCA) is a benign hepatic tumor with poorly characterized risk for spontaneous rupture and malignant transformation. Records from five tertiary hepatobiliary centers were reviewed for all patients treated for LCA from 1997 to 2006. Clinicopathological data were collected and analyzed, and factors that were associated with rupture and/or malignant transformation were assessed by using multivariable logistic regression. A total of 124 patients were analyzed, of which 8 (6.5%) were men; 119 patients underwent resection, and 5 patients had embolic therapy only. Mean patient age was 39 ± 11 years, and 55% had history of hormone use. Rupture occurred in 31 (25%) cases. Ruptured tumors were larger (10.5 ± 4.5 cm vs. 7.2 ± 4.8 cm; p = 0.001), and no tumor <5 cm ruptured. Patients with ruptured LCAs were more likely to require preoperative blood transfusion (32% vs. 9%, p = 0.006), preoperative embolization (16% vs. 1%, p = 0.021), and major (≥3 segments) hepatic resection (65% vs. 32%, p = 0.003). By multivariate analysis, increasing tumor size (odds ratio (OR), 7.8; 95% confidence interval (CI), 2.2-26.3; p < 0.01) and recent (within 6 months) hormone use (OR, 4.5; 95% CI, 1.5–13.3; p < 0.01) remained independently associated with risk of rupture. Five cases (4%) had evidence of underlying malignancy, but none had LCA <8 cm in diameter. In this multicenter analysis of patients with LCAs, risk of rupture correlated with increasing tumor size and recent hormone use. Rupture is associated with greater need for preoperative blood transfusion and major hepatic resection. These data suggest that patients with asymptomatic LCAs approaching 4 cm and those requiring hormonal therapy should undergo surgical therapy.

Radiation Lobectomy: Preliminary Findings of Hepatic Volumetric Response to Lobar Yttrium-90 Radioembolization

Abstract: To describe volumetric changes of “radiation lobectomy,” a manifestation of hepatic parenchymal response to lobar 90Y microsphere radioembolization. Twenty patients exhibiting this phenomenon were identified. Pre- and posttreatment absolute right and left hepatic lobar volume (HLV), relative HLV (rHLV = HLV/total liver volume), and degree of lobar atrophy (DA) or hypertrophy (DH) (DA or DH = |posttreatment rHLV – pretreatment rHLV|) were determined. Laboratory toxicities, tumor response, and patient survival were also assessed. Twenty patients with primary (HCC, n = 17; peripheral cholangiocarcinoma, n = 3) liver malignancies demonstrated findings of radiation lobectomy. Initial absolute right and left HLV was 955 cm3 (range 644–1,842 cm3, rHLV = 57%) and 719 cm3 (range 328–1,387 cm3, rHLV = 43%), respectively. Following 90Y, absolute right HLV decreased to 460 cm3 (range 185–948 cm3, 52% reduction, rHLV = 31%, DA = 26%, P < 0.0001), while absolute left HLV increased to 1,004 cm3 (range 560–1,558 cm3, 40% increase, rHLV = 69%, DH = 26%, P < 0.0001). No grade 3 or 4 bilirubin toxicities were encountered. Tumor response ranged from 55% to 70% by size criteria. Forty-six percent 5-year survival was achieved in HCC patients. Radiation lobectomy following 90Y radioembolization of right lobe tumors manifests extensive contralateral lobar hypertrophy, high response rates, and prolonged survival. This phenomenon was noted in 6.4% (20/315) of the entire cohort and 19.8% (20/101) of patients with unilobar right lobe tumors. Further investigation is necessary to determine contributing factors that may predict this effect.

Surgical Treatment of Resectable and Borderline Resectable Pancreas Cancer: Expert Consensus Statement

Abstract: Margins in pancreatic cancer resection procedures occur at planes where the specimen is separated from surrounding structures or where the pancreas or bowel are divided. These include duodenal/gastric, common bile duct, proximal jejunal, and pancreatic neck transection margins, as well as margins measured “radially” or “tangentially” (anterior and posterior pancreatic surfaces).42 The most important margin is the plane of abutment of the uncinate process with the SMA. Unlike other margins such as the posterior margin where a buffer of fat and areolar tissue lie between the pancreas and the margin, the uncinate process of the pancreas directly contacts the SMA as well as the neural and lymphatic plexus associated with the celiac trunk.26,44 This margin is variously referred to as the uncinate, posterior pancreatic, mesenteric, or retroperitoneal margin. It should be referred to by the more appropriately descriptive term “SMA margin.” Margins can be described clinically and pathologically by R status, where R represents the degree of residual disease.42 R0 means there is neither gross, nor microscopic evidence of cancer at the margin. R1 indicates grossly negative, but microscopically positive disease at the margin. Finally, R2 indicates that gross tumor remains. There is a paucity of detailed literature regarding margins and their influence on survival following pancreatic resections.45,46 Most papers indicate total numbers or percentage of positive margin cases, yet do not provide R status by margin site.47 Nor is the influence of the distance of the margin from edge of the tumor well understood. Accordingly, some investigators have proposed standardization of the process of margin evaluation. This begins in the preoperative period with expert evaluation of the relationship between the tumor and with critical vasculature using high-quality imaging such as dual-phase CT with three-dimensional (3D) reconstruction. A major goal of this evaluation is to eliminate R2 resections prior to surgery. Next, the margins of resected specimens need to be properly oriented by the surgeon and the specimen inked by the pathologist or by the surgeon in the presence of a pathologist. Most importantly, the SMA margin should be evaluated using perpendicular, rather than en face, sampling which should lead to greater specificity, but possibly less sensitivity. It is critical that the surgeon and pathologist reconcile the R status collaboratively in the postoperative period. These principles have been nicely delineated in the current AJCC cancer staging manual (Sixth Edition).42 Clinical Impact of Positive Margins Overall, positive margin rates are reported to range between 15% and 85% and, when present, these are regularly predictive of decreased survival.26,46,48 Unfortunately, in many papers R2 and R1 margin results are lumped, making determination of the individual effect on survival of each of these outcomes is difficult. The SMA margin is most frequently involved (up to 85% of all positive margins). Increased blood loss and large tumor size are predictive of positive margins.26 Outcomes of these historical series indicate that any positive margin will have a survival equivalent to patients with palliative procedures alone.46 However, the most contemporary series (in the setting of regular multimodality therapy, and no R2 resections) shows R1 resection median survival as high as 22 months. This differed significantly from 28 months for R0 resections, but R status did not predict survival on multivariate analysis.26 Surgical Technique The effect of surgical technique on margin positivity has not been rigorously studied. Meticulous dissection of the pancreatic parenchyma off the adventitia of the SMA is advocated, but is not always practically possible.26,44 Procedures have been proposed to minimize positive margins in body and tail tumors (RAMPS), and en bloc resection of adjacent organs to achieve positive margins is also appropriate.49,50 Numerous devices are available to help the surgeon with transection of the pancreas, but none have been rigorously evaluated and none show superiority over the conventional clamp-and-ligate technique. Many surgeons perform frozen section analysis intraoperatively routinely; however, the utility of this practice is undefined in the literature, except in the specific circumstance of intraductal papillary mucinous neoplasm (IPMN).51,52 Obtaining such analysis at the neck and bile duct transection points would seem appropriate in that further tissue may be resected to achieve a clean margin, if positive. However, this is practically not possible on the SMA margin where the artery provides the absolute boundary. Cases with concomitant vein resection may have higher rates of positive margins, especially at the SMA margin, if the patients are not carefully selected. Venous wall invasion occurs up to two-thirds of the time when a decision is made to resect vein. However, despite these findings, on multivariate analysis survival is driven not by the positive margin, but rather by the larger tumor size encountered in these cases.25 It is quite possible that vein resection may, in fact, decrease margin positivity, by facilitating a more controlled tumor resection off of the veins. Pylorus-preserving resection has been shown to have equivalent rates of margin positivity when compared to classical Whipple’s resections, and extended lymphadenectomy procedures, likewise, are not superior in achieving clean margins.17,53 On the other hand, a surgeon’s experience appears to improve performance in this metric, with a threshold of >60 cases executed showing superior outcomes.54 Effect of Multimodality Oncologic Therapy It is possible that combined multimodality (chemo/radiation) therapy may have a positive biologic effect on a positive margin.26,55 The use of preoperative “neoadjuvant” chemoradiation therapy has been studied in this regard and appears to provide lower rates of positive margins, although this does not necessarily equate to improved survival.47 Similarly, focal “boosts” of adjuvant radiation to the positive resection margin may be beneficial. Consensus Statement 1. Nomenclature regarding margins in pancreaticoduodenectomy should be should be standardized. Currently it is vague, confusing, and imprecise. The margin of the pancreas with the SMA should be termed “the SMA margin.” 2. Pathologic assessment of margins is poorly standardized and inconsistently reported. 3. Whipple specimens should be inked, examined, and reported by techniques in conformity with CAP or AJCC guidelines. Manuscripts that assess vascular (usually venous) resection as a prognostic factor for survival must include a system for the assessment of R status. This would include a clear description by the surgeon (in the operative report) of the presence or absence of gross residual disease, and a pathology report that conforms to CAP or AJCC guidelines. 4. The utility of routine intraoperative frozen-section analysis should be determined by carefully planned studies. 5. Safe achievement of an R0 margin is the main surgical objectives of pancreaticoduodenectomy as it is great importance for extended survival. The SMA margin is the most important driver of this outcome. 6. The impact of a microscopically positive (R1) resection on ultimate clinical outcome is uncertain. Multimodality therapy may “recover” a R1 margin and improve survival to that similar to R0 resections.

Evolving Treatment Strategies for Gallbladder Cancer

Abstract: Gallbladder cancer is an uncommon cancer that has traditionally been associated with a poor prognosis. In the era of laparoscopic cholecystectomy, incidental gallbladder cancer has dramatically increased and now constitutes the major way patients present with gallbladder cancer. While patients with incidental gallbladder cancer have a better survival than patients with nonincidental gallbladder cancer, incidental gallbladder cancer can be associated with a varied prognosis. Imaging with computed tomography (CT), magnetic resonance imaging (MRI), and [18]F-fluorodeoxyglucose (FDG) positron emission tomography (PET), as well as diagnostic laparoscopy, all have varying roles in the workup of patients with incidental gallbladder cancer. For patients with T1b, T2, and T3 incidental gallbladder cancer re-resection is generally recommended. At re-exploration, many patients with incidental gallbladder cancer will have residual disease. Definitive oncologic management requires re-resection of the liver, portal lymphadenectomy, and attention to the common bile duct. The extent of the hepatic resection should be dictated by the ability to achieve a microscopically negative (R0) margin. Routine resection of the common bile duct is unnecessary but should be undertaken in the setting of a positive cystic duct margin. If an incidental gallbladder cancer is discovered at the time of surgery, whether the surgeon should directly proceed with a more definitive oncologic operation should depend on the surgeon’s skill-set and experience. Gallbladder cancer has a propensity to recur. Although data for adjuvant therapy following resection are limited, some data do suggest a survival benefit for adjuvant chemoradiation therapy. Management of patients with gallbladder cancer requires a multidisciplinary approach with input from a surgeon skilled in hepatobiliary surgery.

Presenting features of breast cancer differ by molecular subtype.

Abstract: Gene expression profiling of breast cancers identifies distinct molecular subtypes that affect prognosis. Our goal was to determine whether presenting features of tumors differ among molecular subtypes. Subtypes were classified by immunohistochemical surrogates as luminal A (estrogen receptor [ER] and/or progesterone receptor [PR] positive, HER-2−), luminal B (ER and/or PR+, HER-2+), HER-2 (ER and PR−, HER-2+), or basal (ER, PR, HER-2−). Data were obtained from an established, registered database of patients with invasive breast cancer treated at our institution between January 1998 and June 2007. A total of 6,072 tumors were classifiable into molecular subtypes. The χ2 test, analysis of variance, and multivariate logistic regression analysis were used to determine associations between subtype and clinicopathologic variables. The distribution of subtypes was luminal A, 71%; luminal B, 8%; HER-2, 6%; and basal, 15%. Marked differences in age, tumor size, extent of lymph node involvement, nuclear grade, multicentric/multifocal disease, lymphovascular invasion (LVI), and extensive intraductal component were observed among subtypes. When compared with luminal A tumors, those overexpressing HER-2 (luminal B, HER-2) were significantly more likely to manifest nodal involvement, multifocal, extensive intraductal component, and LVI (P < 0.0001). On multivariate analysis, after controlling for patient age, tumor size, LVI, and nuclear grade, HER-2 subtype tumors were 2.0 times more likely to have four or more metastatic lymph nodes (P < 0.0001) and 1.6 times more likely to have multifocal disease (P < 0.0001) compared with patients with luminal A. Tumor presentation varies among molecular subtypes; this information may be useful in selecting local therapy. Neoadjuvant therapy and lymph nodes evaluation before surgery or neoadjuvant therapy are likely to be beneficial in HER-2-overexpressing tumors.

Laparoscopic Versus Open Subtotal Gastrectomy for Adenocarcinoma: A Case–Control Study

Abstract: The aim of this study is to compare technical feasibility and oncologic efficacy of totally laparoscopic versus open subtotal gastrectomy for gastric adenocarcinoma. Laparoscopic gastrectomy for adenocarcinoma is emerging in the West as a technique that may offer benefits for patients, although large-scale studies are lacking. This study was designed as a case-controlled study from a prospective gastric cancer database. Thirty consecutive patients undergoing laparoscopic subtotal gastrectomy for adenocarcinoma were compared with 30 patients undergoing open subtotal gastrectomy. Controls were matched for stage, age, and gender via a statistically generated selection of all gastrectomies performed during the same period of time. Patient demographics, tumor–node–metastasis (TNM) stage, histologic features, location of tumor, lymph node retrieval, recurrence, margins, and early and late postoperative complications were compared. Tumor location and histology were similar between the two groups. Median operative time for the laparoscopic approach was 270 min (range 150–485 min) compared with median of 126 min (range 85–205 min) in the open group (p < 0.01). Hospital length of stay after laparoscopic gastrectomy was 5 days (range 2–26 days), compared with 7 days (range 5–30 days) in the open group (p = 0.01). Postoperative pain, as measured by number of days of IV narcotic use, was significantly lower for laparoscopic patients, with a median of 3 days (range 0–11 days) compared with 4 days (range 1–13 days) in the open group (p < 0.01). Postoperative early complications trended towards a decrease for laparoscopic versus open surgery patients (p = 0.07); however, there were significantly more late complications for the open group (p = 0.03). Short-term recurrence-free survival and margin status was similar between the two groups (p = not significant) with adequate lymph node retrieval in both groups. Laparoscopic subtotal gastrectomy for adenocarcinoma is comparable to the open approach with regard to oncologic principles of resection, with equivalent margin status and adequate lymph node retrieval, demonstrating technically feasibility and equivalent short-term recurrence-free survival. Additional benefits of decreased postoperative complications, decreased length of hospital stay, and decreased narcotic use make this a preferable approach for selected patients.

Lymphedema Microsurgical Preventive Healing Approach: A New Technique for Primary Prevention of Arm Lymphedema After Mastectomy

Abstract: Background The purpose of this manuscript is to assess the efficacy of direct lymphaticvenous microsurgery in the prevention of lymphedema following axillary dissection for breast cancer.

A prospective, multi-institutional study of adjuvant radiotherapy after resection of malignant phyllodes tumors.

Abstract: Background Malignant phyllodes tumors of the breast are unusual neoplasms, with an incidence of approximately 500 cases annually in the United States. Published local recurrence rates after margin-negative breast-conserving resections of borderline malignant and malignant phyllodes tumors are unacceptably high, at 24 and 20%, respectively. It is uncertain whether radiotherapy after resection of phyllodes tumors is beneficial.