Clinical Impact of Lymphadenectomy Extent in Resectable Esophageal Cancer

Esophageal cancer (EC) frequently presents with advanced stages and is associated with high recurrence rates after esophagectomy. The value of an extended lymph node dissection (ELND) remains unclear in this setting. An EC data set was created from the Surveillance, Epidemiology, and End-Results 1973–2003 database. Relationships between the number of lymph nodes (LNs) examined and overall survival (OS) were analyzed. From a cohort of 40,129 EC patients, 5,620 individuals were selected. The median age was 65 (range: 11–102), and 75% were men. The median tumor size was 5.0 cm (0.1–30). On multivariate analysis, total LN count (or negative LN count, respectively) was an independent prognostic variable, aside from age, race, resection status, radiation, T category, N category (all at p < 0.0001), and M category (p = 0.0003). Higher total LN count (>30) and negative LN count (>15) categories were associated with best OS and lowest 90-day mortality (p < 0.0001). The numeric LN effect on OS was independent from nodal status or histology. Greater total and negative LN counts are associated with longer EC survival. Although the mechanism remains uncertain, it does not appear to be limited to stage migration. ELND during potentially curative esophagectomy for EC can be supported by the data.     

Prognostic Significance of Pathologic Nodal Status in Patients with Resected Pancreatic Cancer

Background The purpose of this study was to evaluate the significance of pathologic nodal assessment and extent of nodal metastases on patient outcome in patients with pancreatic adenocarcinoma. Materials and Methods A prospectively maintained pancreatic cancer database was reviewed, and 696 consecutive patients were identified who underwent resection for pancreatic adenocarcinoma between 1995 and 2005. Overall survival was compared to lymph node (LN) status, absolute number of pathologically assessed LN, and LN ratio expressed as the number of positive LN to the total LN assessed. Results Of the 696 patients, 598 (86%) had pancreaticoduodenectomy (PD), and 96 (14%) had distal pancreatectomy (DP). For all patients, median follow-up was 13 months (range, 0–122 months), and estimated 5-year survival was 16%. A total of 243 (35%) patients were LN-negative (N0) and had a median survival of 27 months. When assessed as a continuous variable, the number of pathologically assessed LN did not correlate with survival for N0 patients undergoing either PD or DP. The median survival for the 453 patients with node-positive (N1) disease was 16 months. When analyzed as a continuous variable, the absolute number of positive LNs was a significant predictor of survival for N1 patients with a linear relationship up to eight positive LNs. LN ratio, as a continuous variable, also predicted survival with a linear relationship up to a ratio of 0.35. A ratio of 0.18 was associated with a 19-month median survival and served as the best cutoff, p < 0.01. Conclusions The absolute number of positive LNs and LN ratio are strong predictors of survival for patients with node-positive pancreatic adenocarcinoma. Inadequate surgical lymphadenectomy or pathologic LN assessment understages node-negative patients. Presented in part at the 48th Annual Meeting of the Society for Surgery of the Alimentary Tract, May 22, 2007, Washington, DC.     

The Lymph Node Ratio is the Strongest Prognostic Factor after Resection of Pancreatic Cancer

Introduction  Survival after surgery of pancreatic cancer is still poor, even after curative resection. Some prognostic factors like the status of the resection margin, lymph node (LN) status, or tumor grading have been identified. However, only few data have been published regarding the prognostic influence of the LN ratio (number of LN involved to number of examined LN). We, therefore, evaluated potential prognostic factors in 182 patients after resection of pancreatic cancer including assessment of LN ratio. Methods  Since 1994, 204 patients underwent pancreatic resection for ductal pancreatic adenocarcinoma. Survival was evaluated in 182 patients with complete follow-up evaluations. Of those 182 patients, 88% had cancer of the pancreatic head, 5% of the body, and 7% of the pancreatic tail. Patients underwent pancreatoduodenectomy (85%), distal resection (12%), or total pancreatectomy (3%). Survival was analyzed by the Kaplan–Meier and Cox methods. Results  In all 204 resected patients, operative mortality was 3.9% (n = 8). In the 182 patients with follow-up, 70% had free resection margins, 62% had G1- or G2-classified tumors, and 70% positive LN. Median tumor size was 30 (7–80) mm. The median number of examined LN was 16 and median number of involved LN 1 (range 0–22). Median LN ratio was 0.1 (0–0.79). Cumulative 5-year survival (5-year SV) in all patients was 15%. In univariate analysis, a LN ratio ≥ 0.2 (5-year SV 6% vs. 19% with LN ratio < 0.2; p = 0.003), LN ratio ≥ 0.3 (5-year SV 0% vs. 18% with LN ratio < 0.3; p < 0.001), a positive resection margin (p < 0.01) and poor differentiation (G3/G4; p < 0.03) were associated with poorer survival. In multivariate analysis, a LN ratio ≥ 0.2 (p < 0.02; relative risk RR 1.6), LN ratio ≥ 0.3 (p < 0.001; RR 2.2), positive margins (p < 0.02; RR 1.7), and poor differentiation (p < 0.03; RR 1.5) were independent factors predicting a poorer outcome. The conventional nodal status or the number of examined nodes (in all patients and in the subgroups of node positive or negative patients) had no significant influence on survival. Patients with one metastatic LN had the same outcome as patients with negative nodes, but prognosis decreased significantly in patients with two or more LN involved. Conclusions  Not the lymph node involvement per se but especially the LN ratio is an independent prognostic factor after resection of pancreatic cancers. In our series, the LN ratio was even the strongest predictor of survival. The routine estimation of the LN ratio may be helpful not only for the individual prediction of prognosis but also for the indication of adjuvant therapy and herein related outcome and therapy studies. Presented in part at the 49th Annual Meeting of the Society for Surgery of the Alimentary Tract, May 2008 in San Diego and at the Annual Meeting of the German Cancer Society, February 2008 in Berlin, Germany     

Nodal Microinvolvement in Patients with Carcinoma of the Papilla of Vater Receiving No Adjuvant Chemotherapy

Background  To assess the prognostic significance of nodal microinvolvement in patients with carcinoma of the papilla of Vater. Methods  From 1993 to 2003 at the University Clinic Hamburg, 777 patients were operated upon pancreatic and periampullary carcinomas. The vast majority of patients were operated upon pancreatic ductal adenocarcinoma (n = 566, 73%), followed by carcinomas of the papilla of Vater (n = 112, 14%), pancreatic neuroendocrine carcinomas (n = 39, 5%), intraductal papillary mucinous neoplasms (n = 33, 4%), and distal bile duct carcinomas (n = 27, 3%). Fresh-frozen tissue sections from 169 lymph nodes (LNs) classified as tumor free by routine histopathology from 57 patients with R0 resected carcinoma of the papilla of Vater who had been spared from adjuvant chemotherapy were immunohistochemically (IHC) examined, using a sensitive IHC assay with the anti-epithelial monoclonal antibody Ber-EP4 for tumor cell detection. With regard to histopathology, 39 (63%) of the patients were staged as pT1/pT2, 21 (37%) as pT3/pT4, 30 (53%) as pN0, while 38 (67%) as G1/G2. Results  Of the 169 “tumor-free” LNs, 91 LNs (53.8%) contained Ber-EP4-positive tumor cells. These 91 LNs were from 40 (70%) patients. The mean overall survival in patients without nodal microinvolvement of 35.8 months (median—not yet reached) was significantly longer than that in patients with nodal microinvolvement (mean 16.6; median 13; p = 0.019). Multivariate Cox regression analysis for overall survival revealed that grading was the most significant independent prognostic factor (p = 0.001), followed by nodal microinvolvement (p = 0.013). Conclusions  The influence of occult tumor cell dissemination in LNs of patients with histologically proven carcinoma of the papilla of Vater supports the need for further tumor staging through immunohistochemistry.     

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.     

Radiofrequency Ablation vs. Resection for Hepatic Colorectal Metastasis: Therapeutically Equivalent?

Introduction  The role of ablation for hepatic colorectal metastases (HCM) continues to evolve as ablation technology changes and systemic chemotherapy improves. Our aim was to evaluate the therapeutic efficacy of radiofrequency ablation (RFA) of HCM compared to surgical resection. Methods  A retrospective review of our 1,105 patient prospective hepatic database from August 1995 to July 2007 identified 192 patients with only hepatic resection or only ablation for HCM. Results  Patients who underwent RFA were similar to resection patients based on a similar Fong score (1.8 vs. 2.1 p = 0.28), presence of extrahepatic disease (15% vs. 9% p = 0.19), mean number of hepatic lesions (2.8 vs. 2.1 p = 0.14), and prior chemotherapy (67% vs. 60% p = 0.33). Median time to recurrence was shorter with ablation than resection (12.2 vs. 31.1 months; p < 0.001). Recurrence at the ablation–resection site was more common with ablation than resection occurring 17% vs. 2% (p ≤ 0.001) of the time, respectively. Distant recurrence in the liver was also more common with ablation occurring in 33% of patients vs. 14% for resection (p = 0.002). Conclusions  Surgical resection is associated with a lower chance of recurrence and a longer disease-free interval than RFA and should remain the treatment of choice in resectable HCM.     

Extent of Lymph Node Retrieval and Pancreatic Cancer Survival: Information from a Large US Population Database

Background Operative therapy of pancreatic cancer is associated with poor survival because of high recurrence rates after pancreatectomy. The effect of lymph node (LN) dissection on survival continues to be debated.Methods A pancreatic cancer data set was created through structured queries to the Surveillance, Epidemiology, and End Results 1973 to 2000 database. Stage information was created according to 6th edition American Joint Committee on Cancer tumor-node-metastasis criteria, and the effect of LN number on survival was analyzed.Results Out of a cohort of 20,631 patients with carcinomas of the exocrine pancreas, surgical details were available for 2,787 patients. Procedures included pancreatoduodenectomies (n = 1848; 66%), radical regional pancreatectomies (n = 516; 19%), other partial resections (n = 316; 11%), and total pancreatectomies (n = 107; 4%). For 1666 of these patients with complete clinicopathologic information, the median age was 66 years (range, 22–96 years), with an equal sex ratio. The median number of total LNs examined was 7 (range, 1–52), of positive LNs was 1 (range, 0–34), and of negative LNs was 6 (range, 0–30). Multivariate survival analysis yielded these prognostic variables: number of LNs examined, number of positive LNs, tumor size, extrapancreatic extension, radiotherapy (all P < .0001), and age (P = .0009). The greatest survival differences were observed for negative LN counts of 10 to 15.Conclusions Stage-based survival prediction of pancreatic cancer is strongly influenced by total LN counts and numbers of negative LNs obtained. Although the mechanism remains unclear and could reflect confounding factors (margin status and institutional volume), an attempt to resect and examine at least 15 LNs to yield preferably between 10 and 15 negative LNs seems sensible for curative-intent pancreatectomy.     

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.     

Elevated FGF 23 and phosphorus are associated with coronary calcification in hemodialysis patients

Increased mortality of adult chronic hemodialysis (HD) patients is associated with coronary calcifications (CC), increased serum phosphorus (P), use of calcium (Ca)-containing P-binders, and vitamin D deficiency. Serum concentration of fibroblast growth factor 23 (FGF 23) is markedly elevated in adults receiving dialysis and is independently associated with increased mortality. Although coronary calcifications have been described in pediatric and adult HD patients, no significant association between serum FGF 23 and CC has been reported. In our study, 5/16 patients had CC. Patients with CC were older, had longer dialysis vintage and higher serum P. Serum Ca, total PTH, elemental Ca intake, and calcitriol doses were not different for CC patients. Serum FGF 23 levels were markedly elevated in all patients (mean 4,024, range 874–8,253), but significantly higher in patients with CC (4,247 ± 10,35 vs 2,427 ± 11,92, p = 0.01) and positively correlated with Agatston calcification score (r = 0.69, p = 0.003) and serum P (r = 0.49, p = 0.05). Using multivariate analysis, serum FGF 23 and serum P remained the most significant factors associated with Agatston score. This study confirms the occurrence of CC in pediatric HD patients and is the first to show a significant association between CC and elevated serum FGF 23 in children.     

LCT 13910 C/T polymorphism, serum calcium, and bone mineral density in postmenopausal women

Summary  LCT 13910 CC genotype is associated with lactose intolerance, a condition often resulting in reduced milk intake. Women with the CC genotype were found to have decreased serum calcium and reduced bone mineral density. Introduction  The CC genotype of the 13910 C/T polymorphism of the LCT gene is linked to lactose intolerance and low calcium intake. Methods  We studied 595 postmenopausal women, including 267 osteoporotic, 200 osteopenic, and 128 healthy subjects. Genotyping, osteodensitometry, and laboratory measurements were carried out. Results  Frequency of aversion to milk consumption was 20% for CC genotype and 10% for TT + TC genotypes (p = 0.03). The albumin-adjusted serum calcium was 2.325 ± 0.09 mmol/L for CC genotype and 2.360 ± 0.16 mmol/L for TT + TC genotypes (p = 0.031). Bone mineral density (BMD; Z score) was lower in the CC than TT + TC genotypes, respectively, at the radius (0.105 ± 1.42 vs 0.406 ± 1.32; p = 0.038), at the total hip (−0.471 ± 1.08 vs −0.170 ± 1.09; p = 0.041), and at the Ward’s triangle (−0.334 ± 0.87 vs −0.123 ± 0.82; p = 0.044). Conclusion  LCT 13910 C/T polymorphism is associated with decreased serum calcium level and lower BMD in postmenopausal women. Péter Lakatos and Gábor Speer contributed equally to this work.     

Radiofrequency ablation combined with palliative surgery may prolong survival of patients with advanced cancer of the pancreas

Background and aim The aim of this study is to identify the benefit acquired by the use of radiofrequency ablation in parallel to palliative therapy in patients with advanced cancer of the pancreas. Materials and methods Data on 25 consecutive patients who underwent palliative therapy with or without radiofrequency ablation for unresectable pancreatic cancer were included in this retrospective review. Thirteen patients received palliative therapy alone, whereas 12 patients received palliative therapy plus radiofrequency ablation. Results Overall mean survival rate in patients receiving paliative therapy alone was 13 months and the maximum survival was 30 months. Where radiofrequency ablation was applied, mean survival was estimated at 33 months (p = 0.0048). Stage III and IV patients treated with palliative therapy alone have a mean survival of 15 and 10 months, respectively. All stage III patients receiving radiofrequency ablation are alive at present and maximum survival has reached 38 months (p = 0.0032), whereas stage IV patients who were treated with radiofrequency ablation have an estimated mean survival period of 14 months (p = 0.1095). Conclusion Radiofrequency ablation in parallel to palliative therapy seems to provide survival benefit especially for stage III patients with unresectable pancreatic cancer. Further studies should be conducted to determine the usefulness of radiofrequency ablation in the treatment of advanced pancreatic cancer.     

Safety of Conservative Management of Bile Leakage after Hepatectomy with Biliary Reconstruction

Background  The risks associated with the conservative management of bile leakage after hepatectomy and associated cholangiojejunostomy are not well defined. Aim  The aim of this study was to evaluate incidence and severity of complications associated with bile leakages after liver resection with biliary reconstruction. Patients and methods  Clinical data from 1,034 consecutive patients who underwent liver resection were prospectively collected and reviewed. Bile leakage occurred in 25 out of 119 patients (21.0%) who underwent hepatectomy with biliary reconstruction (group 1) and in 42 out of 915 patients (4.6%) without biliary anastomosis (group 2; p < 0.001). Serum albumin and bilirubin levels were the only preoperative factors significantly different between the two groups. Lymphadenectomy was more frequently performed in patients of group 1 (88% vs 16.7, p < 0.001). Results  Mortality rates were similar in the two groups (8% in group 1 vs 2.3% in group 2, p = 0.28). One or more postoperative complications occurred in 68% in group 1 and in 40.4% in group 2 (p = 0.02). The incidence of sepsis (32% vs 7.1%, p = 0.01), intra-abdominal abscess (12% vs 0, p = 0.04), and abdominal bleeding (28% vs 0, p = 0.006) was significantly higher in group 1. Bile leaks spontaneously healed in 52% of patients in group 1 vs 76.2% in group 2 (p = 0.04). In order to identify independent predictive factors for abdominal bleeding, we compared clinical data of patients with abdominal bleeding (seven patients) and without abdominal bleeding (18 patients) after hepatectomy and biliary reconstruction. Stepwise logistic regression analysis identified the number of reconstructed bile ducts as an independent predictive factor of abdominal bleeding (p = 0.038). Conclusions  Conservative management of bile leakage after liver resection with biliary reconstruction is associated with higher rates of morbidity. The most severe complication is abdominal bleeding, which is related to the number of bile ducts requiring reconstruction.     

Survival Benefit of Radical Prostatectomy in Lymph Node–Positive Patients with Prostate Cancer

Background

Positive lymph node (LN) status is considered a systemic disease state. In prostate cancer, LN-positive diagnosis during pelvic LN dissection (PLND) potentially leads to the abandonment of radical prostatectomy (RP).

Objective

To compare the overall survival (OS) and relative survival (RS; as an estimate for cancer-specific survival) in LN-positive patients with or without RP.

Design, setting, and participants

Between 1988 and 2007, a total of 35 629 men with prostate cancer were identified at the Munich Cancer Registry; of those, 1413 patients had positive LNs.

Intervention

Of these 1413 LN-positive patients, prostatectomy was abandoned in 456 LN-positive patients, whereas 957 underwent RP despite the LN-positive finding.

Measurements

Crucial analyses are based on 938 LN-positive patients (688 with RP and 250 without RP) with complete data regarding age, grade, and prostate-specific antigen (PSA). OS (Kaplan-Meier estimates) and RS are presented, and Cox regression analysis was used to show the influence of predictors such as clinical stage, age at surgery, number of positive LNs, PSA level, grade, and extent of surgery.

Results

Median follow-up was 5.6 yr. OS of patients at 5 yr and 10 yr was 84% and 64%, respectively, with RP and was 60% and 28%, respectively, with aborted RP. The RS of patients at 5 yr and 10 yr was 95% and 86%, respectively, with RP and was 70% and 40%, respectively, with abandoned surgery. There was an imbalance, however, in the number of positive LNs: 17.2% with RP had four or more positive nodes versus 28% in the patient group without RP. In the multivariate model, RP was a strong independent predictor of survival (hazard ratio: 2.04 [95% confidence interval, 1.59–2.63; p < 0.0001]).

Conclusion

LN-positive patients with complete RP had improved survival compared to patients with abandoned RP. These results suggest that RP may have a survival benefit and the abandonment of RP in node-positive cases may not be justified.     

Resection Versus Laparoscopic Radiofrequency Thermal Ablation Of Solitary Colorectal Liver Metastasis

Purpose  There is scant data in the literature regarding radiofrequency thermal ablation (RFA) versus resection of colorectal liver metastases. The aim of this study is to compare the clinical profile and survival of patients with solitary colorectal liver metastasis undergoing resection versus laparoscopic RFA. Methods  Between 1996 and 2007, 158 patients underwent RFA (n = 68) and open liver resection (n = 90) of solitary liver metastasis from colorectal cancer. Patients were evaluated in a multidisciplinary fashion and allocated to a treatment type. Data were collected prospectively for the RFA patients and retrospectively for the resection patients. Results  Although the groups were matched for age, gender, chemotherapy exposure and tumor size, RFA patients tended to have a higher ASA score and presence of extra-hepatic disease (EHD) at the time of treatment. The main indication for referral to RFA included technical reasons (n = 25), patient comorbidities (n = 24), extra-hepatic disease (n = 10) and patient decision (n = 9). There were no peri-operative mortalities in either group. The complication rate was 2.9% (n = 2) for RFA and 31.1% (n = 28) for resection. The overall Kaplan–Meier median actuarial survival from the date of surgery was 24 months for RFA patients with EHD, 34 months for RFA patients without EHD and 57 months for resection patients (p < 0.0001). The 5-year actual survival was 30% for RFA patients and 40% for resection patients (p = 0.35). Conclusions  This study shows that, although patients in both groups had a solitary liver metastasis, other factors including medical comorbidities, technically challenging tumor locations and extra-hepatic disease were different, prompting selection of therapy. With a simultaneous ablation program, higher risk patients have been channeled to RFA, leaving a highly selected group of patients for resection with a very favorable survival. RFA still achieved long-term survival in patients who were otherwise not candidates for resection.     

Analysis of Recurrence Pattern and Its Influence on Survival Outcome After Radiofrequency Ablation of Hepatocellular Carcinoma

Background Radiofrequency ablation (RFA) is an effective local ablation therapy for hepatocellular carcinoma (HCC) with favorable long-term outcome. There is no data on the analysis of recurrence pattern and its influence on long-term survival outcome after RFA in HCC patients. Aim of Study To evaluate the tumor recurrence pattern and its influence on long-term survival in patients with HCC treated with RFA. Patients and Methods From April 2001 to January 2005, 209 patients received RFA using internally cooled electrode as the sole treatment modality for HCC. Among them, 117 patients (56%) had unresectable HCC because of bilobar disease, poor liver function, and/or high medical risk for resection; whereas 92 patients (44%) underwent RFA as the primary treatment for small resectable HCC. The ablation procedure was performed through percutaneous (n = 101), laparoscopic (n = 17), or open approaches (n = 91). The tumor recurrence pattern and long-term survival were analyzed. Multivariate analysis was carried out to identify independent prognostic factors affecting the overall survival of patients. Results The mortality and morbidity rates were 0.9 and 15.7%, respectively. Complete tumor ablation was achieved in 192 patients (92.7%). With a median follow-up period of 26 months, local recurrence occurred in 28 patients (14.5%). Same segment and different segment intrahepatic recurrence occurred in 30 patients (15.6%) and 78 patients (40.6%), respectively. Twenty patients (10.4%) developed distant extrahepatic metastases. The overall 1-, 3-, and 5-year survival rates were 87.2, 66.6, and 42%, respectively. Different segment intrahepatic recurrence and distant recurrence after RFA carried significant poor prognostic influence on overall survival outcome. Using multivariate analysis, Child–Pugh grade (risk ratio [RR] = 2.918, 95% confident interval [CI] 1.704–4.998, p = 0.000), tumor size (RR = 1.231, 95% CI 1.031–1.469, p = 0.021), and pattern of recurrence (risk ratio [RR] = 1.464, 95% CI 1.156–1.987, P = 0.020) were identified as independent prognostic factors for overall survival. Conclusion The tumor recurrence pattern after RFA carries significant prognostic value in relation to overall survival. Long-term regular surveillance and aggressive treatment strategy are required for patients with different segment intrahepatic recurrence to optimize the benefits of RFA.     

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.     

Discordance Between Conventional and Detailed Lymph Node Analysis in Resected Biliary Carcinoma at or Above the Cystic Duct: Are We Understaging Patients?

Background

Analysis of portal lymph node (LN) metastases following resection of biliary carcinomas at or above the cystic duct (BC) is used to select patients for adjuvant therapy, but no guidelines exist and LN yield is low. Some consider analysis of 7 LNs necessary for accurate staging. Conventional LN analysis may understage patients.

Methods

Portal LNs from 38 node-negative patients following resection of BC from 2000 to 2008 were re-examined in detail for occult metastases (OM) using a modified Weaver protocol. Outcomes measured were discordance in LN positivity and patient survival.

Results

On detailed examination, 5 of 38 patients had OM. There was no difference in survival between patients with and without OM (24 vs 17 months; p = .382). There was no association between OM and patient demographics or adverse tumor characteristics. The median LN yield was 3. Of the 27 patients with <7 LNs retrieved, 1 had OM, compared with 4 of 11 patients with ≥7 LNs retrieved (p = .030). OM in these well-staged patients were associated with reduced survival (9 vs 41 months; p = .032).

Conclusions

There is discordance between conventional and detailed LN analysis in resected BC. LN yield ≥7 was associated with OM. The presence of OM may be associated with decreased survival. Conventional LN analysis may understage patients with resected BC.     

Revisiting the Concept of Lymph Node Metastases of Pancreatic Head Cancer: Number of Metastatic Lymph Nodes and Lymph Node Ratio According to N Stage

Background

Some suggest that metastatic lymph node ratio (LNR) may be prognostic of survival in patients with pancreatic cancer. However, this phenomenon was confused by inclusion of node-negative patients in the analysis. The present study was designed to evaluate the prognostic impact of metastatic LNR and the absolute number of metastatic LNs in patients resected for pancreatic cancer.

Methods

Data were collected from 398 patients who underwent curative surgery for pancreatic head cancer at Seoul National University Hospital. Long-term survival was analyzed according to LNR and absolute number of metastatic LNs.

Results

Of the patients, 227 (57.0 %) had LN metastasis. The mean numbers of total retrieved and metastatic LNs were 19.5 and 1.9, respectively, and the mean LNR was 0.11. Median overall survival (OS) of patients was significantly higher in N0 than in N1 patients after curative resection (25.4 vs. 14.8 months, p < 0.001). Median OS was significantly lower in patients with 1 than in those with 0 positive LNs (17.3 vs. 25.4 months, p = 0.001). Among N1 patients, those with 0 < LNR ≤ 0.2 had comparable prognosis than those with >0.2 LNR (median OS 17.2 vs. 12.8 months, p = 0.096), and the number of metastatic LNs did not correlate with median OS (p = 0.365).

Conclusions

The presence of a single positive metastatic LN was associated with significantly poorer OS in patients with pancreatic cancer. When LN metastasis was present, the number of metastatic LNs and LNR had limited prognostic relevance.     

Perioperative Treatment with Infliximab in Patients with Crohn’s Disease and Ulcerative Colitis is Not Associated with an Increased Rate of Postoperative Complications

Purpose  The impact of infliximab (IFX) on postoperative complications in surgical patients with Crohn’s disease (CD) and ulcerative colitis (UC) is unclear. We examined a large patient cohort to clarify whether a relationship exists between IFX and postoperative complications. Methods  A total of 413 consecutive patients—188 (45.5%) with suspected CD, 156 (37.8%) with UC, and 69 (16.7%) with indeterminate colitis—underwent abdominal surgery at the Massachusetts General Hospital between January 1993 and June 2007. One hundred one (24.5%) had received preoperative IFX ≤ 12 weeks before surgery. These patients were compared to those who did not receive IFX with respect to demographics, comorbidities, presence of preoperative infections, steroid use, and nutritional status. We then compared the cumulative rate of complications for each group, which included deaths, anastomotic leak, infection, thrombotic complications, prolonged ileus/small bowel obstruction, cardiac, and hepatorenal complications. Potential risk factors for infectious complications including preexisting infection, pathological diagnosis, and steroid or IFX exposure were further evaluated using logistic regression analysis. Results  Patients were similar with respect to gender (IFX = 40.6% men vs. non-IFX = 51.9%, p = 0.06), age (36.1 years vs.37.8, p = 0.43), Charlson Comorbidity Index (5.3 vs. 5.7, p = 0.25), concomitant steroids (75.3% vs. 76.9%, p = 0.79), preoperative albumin level (3.3 vs. 3.2, p = 0.36), and rate of emergent surgery (3.0% vs. 3.5%, p = 1.00). IFX patients had higher rates of CD (56.4% vs. 41.9%, p = 0.02), concomitant azathioprine/6-mercaptopurine use (34.6% vs. 16.6%, p < 0.0001), and lower rates of intra-abdominal abscess (3.9% vs. 11%, p < 0.05). After surgery, the two groups had similar rates of death (2% vs. 0.3% p = 0.09), anastomotic leak (3.0% vs. 2.9%, p = 0.97), cumulative infections (5.97% vs. 10.1%, p = 1), thrombotic complications (3.6% vs. 3.0%, p = 0.06), prolonged ileus/small bowel obstructions (3.9 vs. 2.8, p = 0.59), cardiac complications (1% vs. 0.6%, p = 0.42), and hepatic or renal complications (1.0 vs. 0.6% p = 0.72). A logistic regression model was then created to assess the impact of IFX, as well as other potential risk factors, on the rates of cumulative postoperative infections. We found that steroids (odds ratio [OR] = 1.2, p = 0.74), IFX (OR 2.5, p = 0.14), preoperative diagnosis of CD (OR = 0.7, p = 0.63) or UC (OR = 0.6, p = 0.48), and preoperative infection (OR = 1.2, p = 0.76) did not affect rates of clinically important postoperative infections. Conclusions  Preoperative IFX was not associated with an increased rate of cumulative postoperative complications. Dr. Sands has received research grants and honoraria for lecturing and consulting from Centocor.     

Increased plasma acylation-stimulating protein in pediatric proteinuric renal disease

Hyperlipidemia has been well recognized as a striking feature of nephrotic syndrome and other renal diseases. However, the underlying pathophysiological mechanisms still have not yet been elucidated. In this study, we evaluated acylation-stimulating protein (ASP) and complement component 3 (C3) in children (n = 48) with various forms of proteinuric renal disease [nephrotic syndrome, acute poststreptococcal infection glomerulonephritis (APSGN), and lupus nephritis (LN)] in comparison with age- and gender-matched controls (n = 279). In children with proteinuric renal disease, various aberrations in plasma lipids were noted, including increased triglyceride, cholesterol, and low-density lipoprotein cholesterol (LDL-C) (all p < 0.0001). Whereas C3 was not altered in children with nephrotic syndrome (1.05 ± 0.05 g/L vs. 1.29 ± 0.04 controls), the decrease was pronounced in children with LN and APSGN (0.42 ± 0.11, p < 0.05 and 0.30 ± 0.06, p < 0.001, respectively). Plasma C3 correlated positively with lipid parameters [triglyceride, cholesterol, LDL-C, apolipoprotein B (apoB), high-density lipoprotein cholesterol (HDL-C) and apoA1] and inversely with total protein, blood urea nitrogen, and creatinine. By contrast, plasma ASP was significantly elevated in all proteinuric renal diseases (101.4 ± 7.1 nmol/L nephrotic syndrome, 90.9 ± 14.1 LN, and 81.8 ± 7.2 APSGN vs. 44.3 ± 1.5 controls, p < 0.05 to p < 0.001), and this increase was correlated with changes in lipid parameters (triglycerides and apoA1). In summary, these results demonstrate alterations in C3 and ASP that may contribute to or compensate for dyslipidemia.