Treatment of Unresectable Cholangiocarcinoma with Gemcitabine-Based Transcatheter Arterial Chemoembolization (TACE): A Single-Institution Experience

Background Survival for patients with unresectable cholangiocarcinoma is reported to range from only 5–8 months without treatment. Systemic chemotherapy has not been shown to significantly improve survival, but newer regimens involving gemcitabine have shown increased response rates. Transcatheter arterial chemoembolization (TACE) has been shown to prolong survival in hepatocellular carcinoma patients, but experience using TACE in the treatment of cholangiocarcinoma is limited. We report our experience treating cholangiocarcinoma with TACE using chemotherapeutic regimens based on the well-tolerated drug gemcitabine. Methods Forty-two patients with unresectable cholangiocarcinoma were treated with one or more cycles of gemcitabine-based TACE at our institution. Chemotherapy regimens used for TACE included: gemcitabine only (n = 18), gemcitabine followed by cisplatin (n = 2), gemcitabine followed by oxaliplatin (n = 4), gemcitabine and cisplatin in combination (n = 14), and gemcitabine and cisplatin followed by oxaliplatin (n = 4). Results Patients were 59 years of age (range 36–86) and received a median of 3.5 TACE treatments (range 1–16). Thirty-seven patients (88%) had central cholangiocarcinoma, and five (12%) had peripheral tumors. Nineteen patients (45%) had extrahepatic disease. Grade 3 adverse events (AEs) after TACE treatments were seen in five patients, whereas grade 4 AEs occurred in two patients. No patients died within 30 days of TACE. Median survival from time of first treatment was 9.1 months overall. Results did not vary by patient age, sex, size of largest initial tumor, or by the presence of extra-hepatic disease. Treatment with gemcitabine–cisplatin combination TACE resulted in significantly longer survival (13.8 months) compared to TACE with gemcitabine alone (6.3 months). Conclusions Our report represents the largest series to date regarding hepatic-artery-directed therapy for unresectable cholangiocarcinoma and provides evidence in favor of TACE as a promising treatment modality in unresectable cholangiocarcinoma. Our results suggest that gemcitabine-based TACE is well tolerated and confers better survival when given in combination therapy (with cisplatin or oxaliplatin) for patients with unresectable cholangiocarcinoma. Presented at the 2007 American Hepato-Pancreato-Biliary Association, Las Vegas, Nevada, April 19–22, 2007 (President’s Plenary Oral Presentation).     

Extrahepatic Disease Should Not Preclude Transarterial Chemoembolization for Metastatic Neuroendocrine Carcinoma

Background

Transarterial chemoembolization (TACE) is often utilized for patients with inoperable neuroendocrine carcinoma liver metastases. Often, metastatic disease is not limited to the liver. The impact of extrahepatic disease (EHD) on outcomes and response after TACE has not been described.

Methods

We reviewed 192 patients who underwent TACE for large hepatic tumor burden, progression of liver metastases, or poorly controlled carcinoid syndrome due to neuroendocrine carcinoma. Demographics, clinicopathologic characteristics, response to TACE, complications, and survival were compared between patients with (n = 123) and without (n = 69) EHD.

Results

Demographics, histopathologic characteristics, and complications were similar between groups. As well, those with and without EHD had similar biochemical (85 vs. 88 %) and radiographic response (76 vs. 79 %) to TACE (all p = NS); however, symptomatic responses were improved in those with EHD (79 vs. 60 %, p = 0.01). The group without EHD had better overall survival compared to those with EHD disease at the time of TACE (median 62 vs. 28 months, p = 0.001).

Discussion

Although patients with EHD from neuroendocrine carcinoma experience shorter overall survival after TACE compared to those without EHD, they had similar symptomatic, biochemical, and radiographic response to TACE. Meaningful response to TACE is still possible in the presence of EHD and should be considered, particularly in those with carcinoid syndrome.     

A Decision Analysis Model Identifies the Interval of Efficacy for Transarterial Chemoembolization (TACE) in Cirrhotic Patients with Hepatocellular Carcinoma Awaiting Liver Transplantation

Introduction For liver transplant candidates with hepatocellular carcinoma (HCC), the ability of neoadjuvant transarterial chemoembolization (TACE) to improve outcomes remains unproven. The objective of our study was to determine if there was a specific time interval where neoadjuvant TACE would decrease the number of HCC patients removed from the pretransplant waitlist. Materials and Methods A decision model was developed to simulate a randomized trial of neoadjuvant treatment with TACE vs. no TACE in 600 virtual patients with HCC and cirrhosis. Transition probabilities for TACE morbidity (1 ± 1%), TACE response rates (30 ± 20%), and disease progression (7 ± 7% per month) were assigned by systematic review of the literature (18 reports). Sensitivity analyses were performed to determine time thresholds where TACE would decrease the number of delisted patients. Results TACE treatment had statistical benefit at waitlist time breakpoints of 4 and 9 months (P < 0.05). When waitlist times were less than 4 months, waitlist attrition was similar (20% vs. 34%, P = 0.08). When waitlist times exceed 9 months, waitlist dropout rates re-equilibrated (33% vs. 46%, P = 0.06). Review of the current literature determined that only those studies reporting on patients with waitlist times between 4 and 9 months found a benefit to neoadjuvant TACE. Conclusions This analysis indicates that the benefit of neoadjuvant TACE may be limited to those patients transplanted from 4 to 9 months from first TACE. These data may help transplant programs to tailor TACE treatments based on predicted waitlist times to achieve optimal resource utilization and improved organ allocation efficiency. Presented at the 7th World Congress of the International Hepato Pancreato Biliary Association Meeting, September 6, 2006, Edinburgh, Scotland.     

比较TACE+微波消融+程序性死亡受体-1与TACE+微波消融治疗原发性肝癌

目的 比较TACE+微波消融（MWA）+程序性死亡受体-1（PD-1）与TACE+MWA治疗原发性肝癌（PHC）的价值。方法 回顾性纳入接受TACE+MWA+PD-1（观察组）或TACE+MWA治疗（对照组）的PHC患者各40例,比较组间基线资料、疗效和并发症。结果 2组患者基线资料差异均无统计学意义（P均>0.05）。观察组与对照组客观缓解率（ORR）分别为90.00%和72.50%,疾病控制率（DCR）分别为97.50%和95.00%;组间差异均无统计学意义（P均>0.05）。观察组与对照组中位总生存期（OS）分别为30.80个月和15.70个月,中位无进展生存期（PFS）分别为23.35个月和6.80个月;观察组OS和PFS均长于对照组（P均<0.05）。组间并发症发生率差异均无统计学意义（P均>0.05）,且均经相关对症治疗后好转。结论 TACE+MWA+PD-1联合治疗PHC效果优于TACE+MWA。     

Impact of Solitary Involved Lymph Node on Outcome in Localized Cancer of the Esophagus and Esophagogastric Junction

Node-positive esophageal cancer is associated with a dismal prognosis. The impact of a solitary involved node, however, is unclear, and this study examined the implications of a solitary node compared with greater nodal involvement and node-negative disease. The clinical and pathologic details of 604 patients were entered prospectively into a database from1993 and 2005. Four pathologic groups were analyzed: node-negative, one lymph node positive, two or three lymph nodes positive, and greater than three lymph nodes positive. Three hundred and fifteen patients (52%) were node-positive and 289 were node-negative. The median survival was 26 months in the node-negative group. Patients (n = 84) who had one node positive had a median survival of 16 months (p = 0.03 vs node-negative). Eighty-four patients who had two or three nodes positive had a median survival of 11 months compared with a median survival of 8 months in the 146 patients who had greater than three nodes positive (p = 0.01). The survival of patients with one node positive [number of nodes (N) = 1] was also significantly greater than the survival of patients with 2–3 nodes positive (N = 2–3) (p = 0.049) and greater than three nodes positive (p < 0001). The presence of a solitary involved lymph node has a negative impact on survival compared with node-negative disease, but it is associated with significantly improved overall survival compared with all other nodal groups.     

Surgical treatment of bone metastases in patients with lung cancer

Lung cancer is the leading cause of cancer mortality. Bone metastases are a common complication in lung cancer. The therapeutic approach and the type of surgical treatment of these lesions have not been clearly defined. Outcome and prognosis of patients with bony metastases and a variety of surgical interventions were analysed retrospectively. In 58 patients we performed 62 surgeries. The most common locations of metastases were the spine (32 patients), the proximal femur (10) and the pelvis (11). Twenty-one patients had a singular and 20 had multiple osseous lesions; 17 showed additional visceral involvement. Nine patients had a local progression of their disease and 49 a systemic progression. Patients with local progression (n = 9) had a better prognosis than the patients with systemic progression (p = 0.0083). Fracture (p = 0.0017) worsened prognosis, whereas the number of bone lesions or the presence of a visceral lesion did not. Patients with small lesions showed a better survival than patients with large lesions (p = 0.02). Ten percent of the patients died within 30 days and 78% within one year after surgery. Fracture of bone due to metastatic lung cancer worsens the prognosis whereas the number of bone lesions, the presence of a visceral lesion and the surgical approach do not.     

Lymph Node Dissection Impact on Staging and Survival of Extrahepatic Cholangiocarcinomas,Based on U.S. Population Data

Cholangiocarcinomas (CC) frequently demonstrate lymphatic spread. We investigated lymph node (LN) counts after resection of extrahepatic CC and survival based on the SEER 1973–2004 database. Out of 20,068 CC patients, 1,518 individuals were selected based on M0 stage and at least one LN examined. Primary cancer sites included gallbladder (29%), extrahepatic bile ducts (26%), and intrapancreatic/ampullary bile ducts (45%); 42% of patients were LN-positive. The median number of LNs examined was four (range 1–39). Median survival was 37 months for LN-negative and 16 months for LN-positive cancers. Multivariate prognostic variables were the number of positive LNs, primary site, age (all at p < 0.0001), gender (p = 0.002), size (p = 0.005), T category (p = 0.009), and total LN count (or number of negative LNs obtained, p = 0.01). The impact of total LN counts was seen in LN-negative (median survival, 1 vs 10 or more LNs examined: 27 vs 51 months, p = 0.002) and LN-positive disease (10 vs 22 months, p < 0.0001). Survival prediction of extrahepatic CCs is strongly influenced by total LN counts and numbers of negative LNs obtained. Although the resulting incremental benefit is small, dissection and examination of 10 or more LNs should be considered for curative intent resections.     

Prognosis and Results After Resection of Very Large (≥10 cm) Hepatocellular Carcinoma

Introduction Few potentially curative treatment options exist besides resection for patients with very large (≥10 cm) hepatocellular carcinoma (HCC). We sought to examine the outcomes and risk factors for recurrence after resection of ≥10 cm HCC. Methods Perioperative and long-term outcomes were examined for 189 consecutive patients from 1993 to 2004 who underwent potentially curative resection of HCC ≥10 cm (n = 24; 13%) vs. those with HCC <10 cm (n = 165; 87%). Disease-free survival (DFS) and overall survival (OS) were determined by Kaplan–Meier analysis and patient, tumor, and treatment characteristics were compared using univariate and multivariate analysis. Results Median follow-up was 34 months. Tumors ≥10 cm were more likely to be symptomatic, of poorer grade, and have vascular invasion (p < 0.05). Twelve patients (50%) underwent an extended resection of more than four hepatic segments or resection of adjacent organs for oncologic clearance (diaphragm-2, inferior vena cava (IVC)-2, median sternotomy-1). Postoperative complications were more common after resection of >10 cm HCC (12/24, 50% vs. 35/165, 21%; p = 0.04). Median DFS was significantly shorter in patients with large HCC (≥10 cm) group compared to patients with smaller HCC (8.4 vs. 38 months; p = 0.001), but overall survival was not different between the two groups (5-year survival 54% vs. 53%; p = 0.43). Seventeen patients (71%) with very large HCC developed recurrences (12 intrahepatic, five systemic); eight of these patients (47%) underwent additional therapy (resection-4, TACE-3, RFA-1). Pathological positive margins and vascular invasion were significant determinants of DFS in tumors ≥10 cm (p < 0.05), but only vascular invasion was an independent risk factor for recurrence after multivariate analysis (HR 0.17; 95% CI: 0.04–0.8). Median OS after recurrence was 24 months. Conclusion Surgical resection is the optimal therapy for very large (≥10 cm) HCC. Although recurrences are common after resection of these tumors, overall survival was not significantly different from patients after resection of smaller HCC in this series. Presented at the 2006 American Hepato-Pancreatico-Biliary Congress, Miami, FL, March 9–12, 2006.     

TACE联合索拉非尼治疗BCLC-C期肝癌的有效性及安全性

目的 观察TACE联合索拉非尼（Sorafenib）治疗巴塞罗那临床肝癌（BCLC）-C期肝细胞癌（HCC）的有效性和安全性。方法 回顾性分析73例BCLC-C期HCC患者,其中35例接受TACE联合索拉菲尼治疗（TACE+Sorafenib组）,38例单纯接受TACE治疗（TACE组）。比较2组治疗1个月后的疗效和不良反应,统计总生存期（OS）及疾病进展时间（TTP）。结果 术后1个月,TACE+Sorafenib组疾病控制率（DCR）高于TACE组（P=0.04）,2组客观缓解率（ORR）差异无统计学意义（P=0.32）。2组主要不良反应包括胃肠道反应、骨髓抑制、皮肤反应及肝功能异常,均无严重不良反应发生;TACE+Sorafenib组皮肤反应、口腔黏膜炎、高血压发生率高于TACE组（P均<0.05）。TACE+Sorafenib组中位OS为13.6个月,中位TTP为6.5个月,均高于TACE组（分别为6.5、3.3个月,P=0.004、0.007）。结论 TACE联合索拉非尼治疗BCLC-C期HCC安全、有效,可改善患者预后。     

Does Microvascular Invasion Affect Outcomes After Liver Transplantation for HCC? A Histopathological Analysis of 155 Consecutive Explants

Macroscopic vascular invasion (macroVI) is associated with poor outcomes after liver transplantation (LT) for hepatocellular carcinoma (HCC). Whether microvascular invasion (microVI) is associated with the same adverse prognosis is unclear. One hundred and fifty-five consecutive patients with confirmed HCC after LT from March 1991 to 2004 at our institution were reviewed. Patients had to satisfy Milan criteria to be accepted for LT. They were followed with surveillance images every 3 months while on the waiting list. Disease-free survival (DFS) and overall survival (OS) were evaluated by Kaplan–Meier analysis. Demographic, tumor, and histopathologic characteristics were tested for their prognostic significance. Median follow-up after LT was 30 months. Overall graft survival rates were 87, 74, and 65% at 1, 3, and 5 years, respectively. All recurrences (22/155, 14%) developed within 4 years after LT with an overall 5-year DFS of 79%. Vascular invasion, either microVI or macroVI, was more likely in patients with multicentric HCC (n ≥ 3, p < 0.001) and larger tumor size >4 cm (p = 0.04). Tumor size >5 cm (p = 0.04), advanced pathological TMN stage (p = 0.007), microVI (p = 0.001), and macroVI (p < 0.001) predicted poor tumor-free survival on univariate analysis, but only macroVI was significant in multivariate analysis (hazard ratio 54.2, 95% confidence interval 11, 266). Furthermore, only macroVI was a significant predictor of mortality after LT (p = 0.01). Macrovascular invasion is strongly associated with high rates of recurrence and diminished survival after LT whereas microVI is not an independent risk factor. Presented at the 2005 American Transplant Congress, Seattle, WA, May 20–23, 2005.     

Association of the macrophage migration inhibitory factor −173*C allele with childhood nephrotic syndrome

Macrophage migration inflammatory factor (MIF) is a proinflammatory cytokine with a unique role as the physiologic counterregulator of the immunosuppressive effects of glucocorticoids. MIF has been implicated in the pathogenesis of glomerular inflammation. The MIF promoter contains a G/C polymorphism that is functionally relevant, with the C allele being associated with higher MIF production and linked to susceptibility to inflammatory diseases. We genotyped the MIF −173 polymorphism in 257 children with idiopathic nephrotic syndrome (INS) and 355 controls. Frequency of carriers of the high-producer MIF −173*C allele was higher in patients with INS (31.7%) than in controls (22.0%) [odds ratio (OR) 1.67, p = 0.006] The MIF −173 C allele was more frequent in steroid-resistant patients (43.5%) compared with steroid responders (22.8%) (OR 2.61, p = 0.0005). This difference was particularly evident in focal segmental glomerulosclerosis patients (OR 14.0, p = 0.002). No association with response to cyclosporin A was found. Carriers of the MIF −173*C allele had a significantly higher probability of end-stage renal disease (ESRD) compared with G/G homozygous patients within 5 years from onset (log rank 5.11 p = 0.024). These results underscore the role of MIF in INS disease progression and in the response to glucocorticoid treatment and suggest that screening of MIF genotype at disease onset may identify patients requiring a more aggressive therapeutic approach. Marina Vivarelli and Leila Emma D’Urbano contributed equally to the work.     

Surgical Outcomes in Esophageal Cancer Patients with Tumor Recurrence After Curative Esophagectomy

This study aimed to identify predictive factors and to evaluate appropriate treatments for recurrence of esophageal cancer after curative esophagectomy. About 166 consecutive patients, who underwent curative esophagectomy, were enrolled between April 1994 and March 2003. Recurrence was classified as loco-regional or distant. Logistic regression analysis was used to identify predictive factors for recurrence. Prognostic factors were evaluated by Log-rank test and Cox proportional hazard regression analysis. The disease-specific 5-year survival was 56.8%. Recurrence was observed in 72 patients (43.4%), with 64 of these occurring within 3 years. The number of metastatic lymph nodes and lymphatic invasion independently predicted recurrence. There were significant differences in time to recurrence and survival time between loco-regional, distant recurrence, and combined recurrence. The 5-year survival time in patients with recurrence was 11.9%, and median survival time was 24 months. There was also a significant difference in survival after recurrence between treatment methods (no treatment vs chemo-radiotherapy, p = 0.0063; chemotherapy, p = 0.0247; and radiotherapy, p < 0.0001). Meticulous, long-term follow-up is particularly necessary in patients with four or more metastatic lymph nodes to achieve early detection of recurrence. Randomized controlled trials should be used to develop effective modalities for each recurrence pattern to improve therapeutic outcomes.     

Multiagent Chemotherapy for Isolated Colorectal Liver Metastases: A Single-centered Retrospective Study

Background  Few studies identifying variables associated with prognosis after resection of colorectal liver metastases (CLM) account for treatment with multiagent chemotherapy (fluoropyrmidines with irinotecan, oxaliplatin, bevacizumab, and/or cetuximab). The objective of this retrospective study was to determine the effect of multiagent chemotherapy on long-term survival after resection of CLM. Methods  Demographics, clinicopathologic tumor characteristics, treatments, and long-term outcomes were reviewed. Results  From 1996 to 2006, 230 patients underwent resection of CLM. Treatment strategies before and after resection included fluoropyrimidine monotherapy (n = 34 and n = 39), multiagent chemotherapy (n = 81 and n = 73), and observation (n = 115 and n = 118). Prehepatectomy treatment strategy was not associated with overall survival. Actuarial 4-year survival was 63%, 39%, and 40% for patients treated with multiagent chemotherapy, fluoropyrimidine monotherapy, and observation after hepatectomy, p = 0.06. Posthepatectomy multiagent chemotherapy (p = 0.04, HR 0.52 [0.27–1.03]), duration of posthepatectomy chemotherapy treatment of 2 months or longer (p = 0.05, HR 0.49 [0.25–0.99]), carcino-embryonic antigen level >10 ng/mL (p = 0.03, HR 2.09, 95% CI [1.32–3.32]), and node positive primary tumor (p = 0.002, HR 1.79 [1.06–3.02]) were associated with overall survival in multivariate analysis. Conclusions  The association of posthepatectomy multiagent chemotherapy with overall survival in this retrospective study indicates the need for prospective randomized trials comparing multiagent chemotherapy and fluoropyrimidine monotherapy for CLM.     

Outcome of Surgical Treatment of Hilar Cholangiocarcinoma

To evaluate surgical results and the effect of adjuvant chemotherapy in cases of hilar cholangiocarcinoma, we retrospectively analyzed 27 consecutive patients who underwent surgical resection (eight bile duct resections, 18 bile duct resections plus hepatectomy, one hepatopancreaticoduodenectomy). There was no operative mortality, and the morbidity was 37%. Curative resection (R0 resection) was achieved in 20 (74%) patients. Overall survival at 3 and 5 years was 44% and 27%, significantly higher than that of 47 patients who did not undergo resection (3.5% and 0% at 3 and 5 years, p < 0.0001). Survival of patients with positive margins (R1/2 resection) was poor; there were no 5-year survivors. However, survival was better than that of patients who did not undergo resection (median survival: 22 vs 9 months, p = 0.0007). Univariate analysis identified lymph node metastasis as a negative prognostic factor (p = 0.043). Median survival of patients who underwent adjuvant chemotherapy was significantly longer than that of patients who did not (42 vs. 22 months, p = 0.0428). Resection should be considered as the first option for hilar cholangiocarcinoma. There appears to be a survival advantage even in patients with cancer-positive margins. Adjuvant chemotherapy may increase long-term survival.     

Cervical Nodal Metastasis from Intrathoracic Esophageal Squamous Cell Carcinoma is not Necessarily an Incurable Disease

Background  It remains controversial if metastatic cervical lymph nodes in patients with intrathoracic esophageal cancer signify distant metastases and are therefore incurable or if they should be regarded as regional spread with a potential for cure. Material and Methods  Patients with intrathoracic esophageal squamous cell carcinoma managed from 1995 to 2007, in whom metastatic cervical lymph node spread was confirmed by fine needle aspiration cytology, were studied. Treatment strategies and outcome were reviewed. Results  There were 109 patients, of whom 98 were men. Median age was 62 years (range, 34–88). Excluding those who underwent primarily palliative treatments, there were two main groups: 22 who had upfront chemoradiation therapy and subsequent esophagectomy ± cervical lymphadenectomy and 46 who had chemoradiation only. Significant downstaging occurred in 29 of the 68 patients (42.6%), of whom eight (11.8%) had complete pathological/clinical response. There was no mortality after esophagectomy. Median survival of patients with chemoradiation plus esophagectomy was 34.8 months compared to those with no surgery at 9.9 months, (p < 0.001). Patients with stage IV disease at presentation by virtue of nodal disease survived longer than those with the same stage because of systemic organ metastases: 9.3 vs. 3 months, (p < 0.001). Conclusions  Prognosis of patients with metastatic cervical nodes was not uniformly dismal. Up to 20% had reasonable survival after chemoradiation and surgical resection. Stage IV disease should be revised to segregate those with nodal and systemic metastases.     

Echogenic Appearance of Colorectal Liver Metastases on Intraoperative Ultrasonography is Associated with Survival After Hepatic Resection

Survival after resection of colorectal liver metastases has traditionally been associated with clinicopathologic factors. We sought to investigate whether echogenicity of colorectal liver metastasis as assessed by intraoperative ultrasound (IOUS) was a prognostic factor after hepatic resection. Prospective data on tumor IOUS appearance were collected in 84 patients who underwent hepatic resection for colorectal liver metastasis. Images were digitally recorded, blindly reviewed, and scored for echogenicity (hypo-, iso-, or hyperechoic). The median tumor number was 1 and the median tumor size was 5.0 cm. At the time of surgery, the IOUS appearance of the colorectal liver metastases were hypoechoic in 35 (41.7%) patients, isoechoic in 37 (44.0%) patients, and hyperechoic in 12 (14.3%) patients. Traditional clinicopathologic prognostic factors were similarly distributed among the three echogenicity groups (all p > 0.05). Patients with a hypoechoic lesion had a significantly shorter median survival (30.2 months) compared with patients who had either an isoechoic (53.2 months) or hyperechoic (42.3 months) lesion (p = 0.005). The 5-year survival after hepatic resection of colorectal liver metastasis was also associated with the echogenic appearance of the lesion (hypoechoic 14.4 vs isoechoic 37.4 vs hyperechoic 46.2%) (p < 0.05). Intraoperative ultrasound echogenicity should be considered a prognostic factor after hepatic resection of metastatic colorectal cancer. This study was presented at the 47th annual meeting of The Society for Surgery of the Alimentary Tract, Los Angeles, CA, USA, 22 May 2006.     

CA 19-9 Velocity Predicts Disease-Free Survival and Overall Survival After Pancreatectomy of Curative Intent

Introduction  This study was undertaken to correlate serum CA 19-9 levels and CA 19-9 velocity with disease-free and overall survival after pancreatectomy for adenocarcinoma. Methods  From 1997 to 2002, 96 patients underwent pancreatectomy without adjuvant chemotherapy as the control arm of a large randomized prospective adjuvant therapy trial. After resection, CA 19-9 levels were drawn at baseline, 4 weeks, and 12-week intervals thereafter. CA 19-9 velocity denotes rate of change in CA 19-9 levels over a 4-week period. Postoperative baseline CA 19-9 levels and CA 19-9 velocity were correlated with disease-free and overall survival. Data are presented as median (mean ± SD). Results  Disease-free survival was 7 months (14 ± 13.7), and overall survival was 12 months (19 ± 14.3) with 24 (25%) patients alive at 41 months (39 ± 7.8). Baseline CA 19-9 levels and CA 19-9 velocity predicted disease-free (p < 0.01) and overall survival (p < 0.01). CA 19-9 velocity was a better predictor of overall survival than baseline CA 19-9 (p < 0.001). CA 19-9 velocity at disease progression was 131 U/ml/4-weeks (1,684 ± 4,474.8) vs. 1 U/ml/4-weeks (1 ± 3.8) at 22 months for patients without disease progression (p < 0.001). Conclusions  CA 19-9 velocity predicts imminent disease progression after resection of pancreatic adenocarcinoma and is a better predictor of overall survival than baseline CA 19-9 levels. CA 19-9 velocity is a reliable and relatively inexpensive means of monitoring patients after resection of pancreatic cancer and should be considered in all patients enrolled in clinical trials as well as patients receiving adjuvant therapy.     

Revisional vs. Primary Roux-en-Y Gastric Bypass—a Case-matched Analysis

With the increase in bariatric procedures performed, revisional surgery is now required more frequently. Roux-en-Y gastric bypass (RYGB) is considered to be the gold standard revision procedure. However, data comparing revisional vs. primary RYGB is scarce, and no study has compared non-resectional primary and revisional RYGB in a matched control setting. Analysis of 61 revisional RYGB that were matched one to one with 61 primary RYGB was done. Matching criteria were preoperative body mass index, age, gender, comorbidities and choice of technique (laparoscopic vs. open). After matching, the groups did not differ significantly. Previous bariatric procedures were 13 gastric bands, 36 vertical banded gastroplasties, 10 RYGB and two sleeve gastrectomies. The indication for revisional surgery was insufficient weight loss in 55 and reflux in 6. Intraoperative and surgical morbidity was not different, but medical morbidity was significantly higher in revisional procedures (9.8% vs. 0%, p = 0.031). Patients undergoing revisional RYGB lost less weight in the first two postoperative years compared with patients with primary RYGB (1 month, 14.9% vs. 29.7%, p = 0.004; 3 months, 27.4% vs. 51.9%, p = 0.002; 6 months, 39.4 vs. 70.4%, p < 0.001; 12 months, 58.5% vs. 85.9%, p < 0.001; 24 months, 60.7% vs. 90.0%, p = 0.003). Although revisional RYGB is safe and effective, excess weight loss after revisional RYGB is significantly less than following primary RYGB surgery. Weight loss plateaus after 12 months follow-up.     

Anastomotic Leakage is Associated with Poor Long-Term Outcome in Patients After Curative Colorectal Resection for Malignancy

The impact of anastomotic leakage on long-term outcomes after curative surgery for colorectal cancer has not been well documented. This study aimed to investigate the effect of anastomotic leakage on survival and tumor recurrence in patients who underwent curative resection for colorectal cancer. Prospectively collected data of the 1,580 patients (904 men) of a median age of 70 years (range: 24–94), who underwent potentially curative resection for colorectal cancer between 1996 and 2004, were reviewed. Cancer-specific survival and disease recurrence were analyzed using Kaplan Meier method, and variables were compared with log rank test. Cox regression model was used in multivariate analysis. The cancer was situated in the colon and the rectum in 933 and 647 patients, respectively. Anastomotic leakage occurred in 60 patients (clinical leakage: n = 48; radiological leak: n = 12). The leakage rate was significantly higher in patients with surgery for rectal cancer (6.3 vs 2.0%, p < 0.001). The 5-year cancer-specific survivals were 56.9% in those with leakage and 75.9% in those without leakage (p = 0.012). The 5-year systemic recurrence rates were 48.4 and 22.6% in patients with and without anastomotic leak, respectively (p = 0.001), whereas the 5-year local recurrence rates were 12.9 and 5.7%, respectively (p = 0.009). Anastomotic leakage remained an independent factor associated with a worse cancer-specific survival (p = 0.043, hazard ratio: 1.63, 95% CI: 1.02–2.60) and a higher systemic recurrence rate (hazard ratio: 1.94, 95% CI: 1.23–3.06, p = 0.004) on multivariate analysis. In rectal cancer, anastomotic leakage was an independent factor for a higher local recurrence rate (hazard ratio: 2.55, 95% CI: 1.07–6.06, p = 0.034). In conclusion, anastomotic leakage is associated with a poor survival and a higher tumor recurrence rate after curative resection of colorectal cancer. Efforts should be undertaken to avoid this complication to improve the long-term outcome. This work was presented in the plenary session of the 47th Annual Meeting of the Society for Surgery of the Alimentary Tract at the Digestive Disease Week in Los Angeles on 22 May 2006.     

Efficacy of Preoperative Combined 18-Fluorodeoxyglucose Positron Emission Tomography and Computed Tomography for Assessing Primary Rectal Cancer Response to Neoadjuvant Therapy

Purpose Efficacy of F-18 fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) for determining neoadjuvant therapy response in rectal cancer is not well established. We sought to evaluate serial FDG-PET/CT for assessing tumor down-staging, percentage residual tumor, and complete response or microscopic disease with rectal cancer neoadjuvant therapy. Methods Patients with rectal cancer undergoing neoadjuvant therapy, definitive surgical resection, and FDG-PET/CT before and 4–6 weeks after neoadjuvant treatment were included. Tumors were evaluated pretreatment and on final pathology for size and stage. FDG-PET/CT parameters assessed were visual response score (VRS), standardized uptake value (SUV), PET-derived tumor volume (PETvol), CT-derived tumor volume (CTvol), and total lesion glycolysis (δTLG). Results Twenty-one rectal cancer patients over 3 years underwent neoadjuvant treatment, serial FDG-PET/CT, and resection. Complete response or microscopic disease (n = 7, 33%) was associated with higher ΔCTvol (AUC = 0.82, p = 0.004) and ΔSUV (AUC = 0.79, p = 0.01). Tumor down-staging (n = 14, 67%) was associated with greater ΔPETvol (AUC = 0.82, p < 0.001) and ΔSUV (AUC = 0.82, p < 0.001). Pathologic lymph node disease (n = 7, 33%) correlated with ΔCTvol (AUC = 0.75, p = 0.03) and ΔPETvol (AUC = 0.70, p = 0.08). Conclusion FDG-PET/CT parameters were best for assessing tumor down-staging and percentage of residual tumor after neoadjuvant treatment of rectal cancer and can potentially assist in treatment planning. This work was presented in the plenary session of the 47th Annual Meeting of the Society for Surgery of the Alimentary Tract at the Digestive Disease Week in Los Angeles, CA on 24 May 2006.