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This article describes the epidemiology, risk factors, diagnostic imaging tools, and operative management of gallbladder cancer. The rarity of gallbladder cancer coupled with the prevalence of benign gallbladder disease mean that most patients undergo initial procedures that violate tumor planes, complicating attempts at future oncologic resection. Fortunately, a previous laparoscopic or open cholecystectomy does not lessen survival after definitive surgical extirpation. Large retrospective and underpowered prospective studies have suggested benefit to adjuvant chemotherapy or radiotherapy; however, these results need to be confirmed with large prospective randomized trials.

Due to the prevalence of tumor chemoresistance, the clinical response of advanced non-small cell lung cancer (NSCLC) to chemotherapy is poor. We suppressed tumor resistance to doxorubicin (Dox) in A549 cells, a human NSCLC cell line, both in vitro and in vivo in a lung tumor xenograft model, using a novel adenoviral expression system to deliver an RNA aptamer (A-p50) that specifically inhibits nuclear factor-kappaB (NF-kappaB) activation. By achieving selective, targeted, and early inhibition of NF-kappaB activity, we demonstrate that NF-kappaB plays a critical role in Dox-induced chemoresistance by regulating genes involved in proliferation (Ki-67), response to DNA damage (GADD153), antiapoptosis (Bcl-XL), and pH regulation (CA9). This Dox-induced NF-kappaB activation and subsequent chemoresistance is dependent on expression of p53. We also demonstrate that NF-kappaB promotes angiogenesis in the presence of Dox via the hypoxia-inducible factor-1alpha/vascular endothelial growth factor (HIF-1alpha/VEGF) pathway, revealing a previously unknown mechanism of NSCLC resistance to Dox. These studies provide important insights into the mechanisms of Dox-induced chemoresistance, and they demonstrate a novel, effective, and clinically practical strategy for interfering with these processes.

Background: The safety of simultaneous resections of colorectal cancer and synchronous liver metastases (SCRLM) is not established. This multi-institutional retrospective study compared postoperative outcomes after simultaneous and staged colorectal and hepatic resections., Methods: Clinicopathologic data, treatments, and postoperative outcomes from patients who underwent simultaneous or staged colorectal and hepatic resections at three hepatobiliary centers from 1985-2006 were reviewed., Results: 610 patients underwent simultaneous (n = 135) or staged (n = 475) resections of colorectal cancer and SCRLM. Seventy staged patients underwent colorectal and hepatic resections at the same institution. Simultaneous patients had fewer (median 1 versus 2) and smaller (median 2.5 versus 3.5 cm) metastases and less often underwent major (> or = three segments) hepatectomy (26.7% versus 61.3%, p < 0.05). Combined hospital stay was lower after simultaneous resections (median 8.5 versus 14 days, p < 0.0001). Mortality (1.0% versus 0.5%) and severe morbidity (14.1% versus 12.5%) were similar after simultaneous colorectal resection and minor hepatectomy compared with isolated minor hepatectomy (both p > 0.05). For major hepatectomy, simultaneous colorectal resection increased mortality (8.3% versus 1.4%, p < 0.05) and severe morbidity (36.1% versus 15.1%, p < 0.05). Combined severe morbidity after staged resections was lower compared to simultaneous resections (36.1% versus 17.6%, p = 0.05) for major hepatectomy but similar for minor hepatectomy (14.1% versus 10.5%, p > 0.05). Major hepatectomy independently predicted severe morbidity after simultaneous resections [hazard ratio (HR) = 3.4, p = 0.008]., Conclusions: Simultaneous colorectal and minor hepatic resections are safe and should be performed for most patients with SCRLM. Due to increased risk of severe morbidity, caution should be exercised before performing simultaneous colorectal and major hepatic resections.

Background: The role of hepatic resection for metastatic squamous cell carcinoma (SCC) remains unknown. The current study evaluates the role of hepatic resection in patients with metastatic SCC to the liver., Methods: Between 1988 and 2006, 52 patients underwent hepatic resection of metastatic SCC at eight major cancer centers. Clinicopathologic factors were analyzed with regard to disease-free survival (DFS) and overall survival (OS)., Results: Primary SCC site was anal (n = 27), head/neck (n = 12), lung (n = 4), esophagus (n = 2), and other (n = 7). Treatment of primary SCC was chemotherapy +/- radiotherapy alone (n = 29), chemotherapy +/- radiotherapy + surgery (n = 15), or surgery alone (n = 8). Forty-seven patients underwent resection alone, 2 resection + radiofrequency ablation (RFA), and 3 RFA only. At last follow-up, 33 (63.5%) patients had recurred. The median time to recurrence was 9.8 months, and 5-year DFS was 18.6%. Factors associated with reduced DFS were liver tumor size > 5 cm (hazard ratio (HR) = 2.02) and positive surgical margin (HR = 2.33). The overall median survival after hepatic resection was 22.3 months and 5-year actuarial OS was 20.5%. Risk factors associated with worse overall survival included synchronous disease (HR = 4.09), hepatic metastasis > 5 cm (HR = 1.71) and positive surgical resection margin (HR = 1.83)., Conclusions: The majority of patients will recur following hepatic resection of SCC. Long-term survival, however, can be achieved following surgical resection of SCC liver metastasis, especially in patients who present with limited metachronous disease amenable to margin negative resection.

Background: Theoretical benefits of preoperative chemoradiation therapy (preop CRT) for pancreatic cancer include improved efficacy, resectability, and patient selection. The goal of this study was to evaluate the applicability of a nomogram, which was developed for patients undergoing resection without preop CRT and which incorporates several post-resection pathological factors, to a population of patients who received preop CRT prior to resection., Methods: From 1994 to 2004, 82 patients with biopsy-proven, radiographically localized adenocarcinoma of the pancreatic head underwent preop CRT followed by pancreaticoduodenectomy (PD); 50 concurrent patients underwent PD without preop CRT. Mean nomogram-predicted disease-specific survival (DSS) rates were compared with observed DSS rates from the time of resection., Results: Despite having more locally advanced tumors on initial staging (21 vs. 8%; P < .05), patients who received preop CRT had smaller resected tumors (mean 2.3 vs. 3.1 cm; P < .01), were less likely to have T3 tumors (54 vs. 80%, P < .01), were less likely to have positive lymph nodes (29 vs. 58%, P < .01), and had fewer positive lymph nodes (mean .4 vs. 1.9, P < .01), all factors that imply treatment effect and favorably impact on nomogram-predicted DSS. Observed DSS was similar to predicted DSS in both groups., Conclusions: The similarity in observed and predicted DSS following resection in patients who received preop CRT suggests that the effects of preop CRT-whether treatment, selection, or no effect-are reflected by the nomogram. The ability of the nomogram to evaluate the effects of preop CRT on survival is limited by the potential effects of preop CRT on factors within the nomogram.

Background: Resection of melanoma metastatic to the liver remains controversial. We evaluated the efficacy of hepatic resection in patients with metastatic ocular and cutaneous melanoma and assessed factors that could affect survival after resection., Methods: Forty patients with hepatic melanoma metastasis underwent resection at four major hepatobiliary centers. Clinicopathologic factors were evaluated with regard to recurrence and survival by using chi(2) and log-rank tests., Results: The primary tumor was ocular in 16 patients and cutaneous in 24. The median disease-free interval from the time of primary tumor treatment to hepatic metastasis was the same for both groups (ocular, 62.9 months; cutaneous, 63.1 months; P = .94). Most patients underwent either an extended hepatic resection (37.5%) or hemihepatectomy (22.5%). Twenty-six patients (65%) received perioperative systemic therapy. Thirty (75.0%) of 40 patients developed tumor recurrence. The median time to recurrence after hepatic resection was 8.3 months (ocular, 8.8 months; cutaneous, 4.7 months; P = .3). Patients with primary ocular melanoma were more likely to experience recurrence within the liver (53.3% vs. 17.4%; P = .015), whereas patients with a cutaneous primary tumor more often developed extrahepatic involvement. The 5-year survival rate for patients with a primary ocular melanoma was 20.5%, whereas there were no 5-year survivors for patients with cutaneous melanoma (P = .03)., Conclusions: Patterns of recurrence and prognosis after resection of hepatic melanoma metastasis differ depending on whether the primary melanoma is ocular or cutaneous. Resection should be performed as part of a multidisciplinary approach, because recurrence is common.

Background: Neoadjuvant chemoradiotherapy (neo-CRT) is being used with increasing frequency for periampullary tumors, but how it alters the complication rate of pancreaticoduodenectomy (PD) is unclear., Methods: A retrospective analysis was conducted of 79 patients with periampullary malignancies who received 5-fluorouracil-based neo-CRT followed by PD., Results: There was no difference in mortality between PD after neo-CRT (3.8%) and conventional PD for either malignant (4.5%) or benign (2.2%) disease. Focusing only on patients with malignancy, the neo-CRT group had a significantly lower pancreatic leak rate than the conventional group (10% vs. 43%; P < .001). Intra-abdominal abscesses were less common in the neo-CRT group (8.8% vs. 21%; P = .019), and there was one (1.2%) amylase-rich abscess in neo-CRT group, compared with eight (12%) in the conventional group. In addition, two patients in the conventional group died of leak-associated sepsis, compared with none in the neo-CRT group. Multivariate analysis revealed that neoadjuvant chemoradiation (odds ratio, .15) was the most significant factor associated with a reduced risk of pancreatic leak., Conclusions: Neo-CRT does not increase the mortality or morbidity of PD. In contrast, neo-CRT was associated with a marked reduction in the incidence of pancreatic leak, as well as leak-associated morbidity and mortality.

Background: Neoadjuvant (preoperative) chemoradiotherapy (CRT) for pancreatic cancer offers theoretical advantages over the standard approach of surgery followed by adjuvant CRT. We hypothesized that histological responses to CRT would be significant prognostic factors in patients undergoing neoadjuvant CRT followed by resection., Methods: Since 1994, 193 patients with biopsy-proven pancreatic adenocarcinoma have completed neoadjuvant CRT, and 70 patients have undergone resection. Specimens were retrospectively examined by an individual pathologist for histological responses (tumor necrosis, tumor fibrosis, and residual tumor load) and immunohistochemical staining for p53 and epidermal growth factor receptor. Factors influencing overall survival were analyzed with the Kaplan-Meier (univariate) and Cox proportional hazards (multivariate) methods., Results: The estimated overall survival (median +/- SE) in the entire group of patients undergoing resection was 23 +/- 4.2 months, with an estimated 3-year survival of 37% +/- 6.6% and a median follow-up of 28 months. Complete histological responses occurred in 6% of patients. Overexpression of p53 was more common in patients with large residual tumor loads. Tumor necrosis was an independent negative prognostic factor, as were positive lymph nodes, a large residual tumor load, and poor tumor differentiation., Conclusions: Histological response to neoadjuvant CRT--as measured by residual tumor load--may be useful as a surrogate marker for treatment efficacy. Characterization of the tumor cells that survive neoadjuvant CRT may help us to identify new or more appropriate targets for systemic therapy.

Objective: We sought to evaluate the accuracy of dual-phase MDCT angiography for assessing the liver before hepatic resection and to compare 2D and 3D images for quality and arterial branch visualization., Materials and Methods: Sixty-three patients with colorectal metastases (n = 30), hepatocellular carcinomas (n = 13), giant hemangiomas (n = 5), and other lesions (n = 15) underwent dual-phase MDCT using either a LightSpeed QX/i 4-MDCT (n = 31) or LightSpeed QX/i Ultra 8-MDCT (n = 32) scanner. Contrast material (150 mL of Isovue 370 [iopamidol]) was injected at a rate of 5 mL/sec. The arterial phase images were rendered on a workstation to obtain 3D MDCT angiograms that were assessed by two reviewers who were blinded to the surgical findings. Arterial anatomy was categorized according to the Michels classification. The reviewers assessed the 2D and 3D images for quality, arterial branch visualization, and differences between the 4- and 8-MDCT images. In the 43 patients who underwent resection, imaging findings were correlated with intraoperative findings., Results: The anatomy of hepatic arteries in the 63 patients was classified as follows: Michels type I, 51 patients (80.9%); type III, four patients (6.3%); type V, five patients (7.9%); and types VII, VIII, and IX, one patient (1.6%) each. In 40 (93%) of 43 patients, the surgical findings concurred with MDCT findings. Three discrepancies were due to failure to identify small accessory left hepatic arteries. Branch visualization and image quality of the 2D images were superior to those of the 3D images. No significant difference was found between the 4- and 8-MDCT images in branch visualization and image quality., Conclusion: Three-dimensional MDCT angiography is accurate for classification of hepatic arterial anatomy before hepatic resection. Although 2D data sets show small arteries to better advantage than 3D MDCT angiograms, the 3D MDCT angiograms provide a useful overview of hepatic anatomy.