Response to Neoadjuvant Chemotherapy Does Not Predict Overall Survival for Patients With Synchronous Colorectal Hepatic Metastases

Objective  We investigated the relation between response to neoadjuvant chemotherapy and overall survival (OS) in patients with colorectal liver metastases (CLM). Background  It has previously been reported that patients with synchronous CLM whose disease progresses while receiving neoadjuvant chemotherapy or who do not receive neoadjuvant chemotherapy experience worse survival than patients whose disease responds to neoadjuvant chemotherapy. Methods  By means of a prospectively maintained surgical database, between 1995 and 2003, we identified 111 patients with a synchronous CLM who received neoadjuvant chemotherapy before hepatic resection. The disease of all 111 patients was deemed resectable, and patients underwent hepatic resection with curative intent. Results  The median OS after liver resection was 62 months, with a median follow-up of 63 months. Median OS was similar between the three study groups classified by response to neoadjuvant chemotherapy (complete or partial response, 58 months; stable disease, 65 months; and disease progression, 61 months; P = .98). By univariate analysis, carcinoembryonic antigen level after liver resection of <5 ng/dL, size of metastatic lesion of ≤5 cm, lymph node–negative primary tumor, and disease-negative margins were associated with improved survival. Patients in the disease progression group had more positive margins and metastases >5 cm in size than patients in the complete or partial response group and the stable disease group. Patients whose tumor progressed but who received postoperative hepatic arterial infusion had a trend toward improved survival compared with those who did not receive hepatic arterial infusion (70% vs. 50% at 3 years, permutation log rank test P = .12). Conclusions  Response to neoadjuvant chemotherapy did not correlate with OS even after controlling for margins, stage of primary tumor, and postoperative carcinoembryonic antigen level. Postoperative salvage treatment may have helped the survival of some patients.     

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.     

Survival Outcomes of Patients with Colorectal Liver Metastases Following Hepatic Resection or Ablation in the Era of Effective Chemotherapy

The outcome of patients with colorectal liver metastases (CLM) undergoing surgical resection in the era of effective chemotherapy is not widely reported. In addition, factors associated with disease-specific survival (DSS) in a contemporary series of patients are not well defined. Clinical, pathologic, and outcome data for 64 patients with CLM treated by a single surgeon in a multidisciplinary setting from February 2002 to October 2007 were examined. Hepatic resection was combined with radiofrequency ablation (RFA) in 23 (36%) cases. Secondary or tertiary resection was undertaken in 12 (19%) patients. Synchronous CLM were noted in 25 (39%) cases. Neoadjuvant chemotherapy was given to 41 (64%) patients. Following hepatic resection, adjuvant chemotherapy was administered in 52 (81%) cases. There was one (2%) operative mortality. One or more complications were noted in 24 (38%) patients. Median length of hospital stay was 7 (2–7) days. Five-year DSS and overall survival were 72% and 69%, respectively. Bilobar disease (p < 0.001), local tumor extension (p = 0.02), response to neoadjuvant chemotherapy (p = 0.005), preoperative portal vein embolization (p = 0.05), number of hepatic lesions (p = 0.03), positive resection margin (p < 0.001), and node-positive primary disease (p = 0.001) were prognostically significant factors on univariate analysis. On multivariate analysis, bilobar disease (p = 0.02) and local tumor extension (p = 0.02) were the only two independent prognostic factors. We conclude that, in patients with CLM, a multidisciplinary approach encompassing an aggressive surgical policy achieves excellent 5-year survival results with acceptable operative morbidity and mortality. Bilobar disease and local extrahepatic extension of cancer appear to be independent prognostic factors for long-term survival.     

Distal Bowel Surgical Margin Shorter than 1 cm After Preoperative Radiation for Rectal Cancer: Is It Safe?

Background  The primary end-point of our randomized trial was sphincter preservation. The secondary aim was to evaluate whether distal bowel clearance ≤1 cm is safe after radiation. Methods  The study randomized 312 patients with cT3-4 resectable low-lying and mid-rectal cancer to receive either preoperative irradiation (5 × 5 Gy) with immediate total mesorectal excision (TME) or chemoradiation (50.4 Gy, bolus 5-fluorouracil and leucovorin) with delayed TME. After anterior resection, pathologists prospectively measured macroscopic and microscopic distal bowel clearance. Results  Macroscopic and microscopic distal bowel clearance, distal intramural spread, sphincter preservation, local control, disease-free survival, and overall survival did not differ in the two randomized groups. Pooled analysis of the two groups showed that the incidence of local recurrence at 4 years (median follow-up) for patients with macroscopic clearance ≤1 cm (n = 42) and >1 cm (n = 124) was 11.3% and 15.4%, respectively (P = 0.514); the hazard ratio (HR) was 0.70, and the 95% confidence interval (CI) was 0.23–2.07. The corresponding values for patients with microscopic clearance ≤1 cm (n = 51) and >1 cm (n = 101) were 9.6% and 17.6% (P = 0.220; HR 0.51; 95% CI 0.17–1.53). Conclusion  After preoperative radiotherapy, distal bowel clearance ≤1 cm did not compromise local control.     

Comparison of long-term survival outcome after curative hepatectomy between selected patients with non-colorectal and colorectal liver metastasis: A propensity score matching analysis

BackgroundLiver resection is an established treatment of choice for colorectal liver metastasis (CLM). However, the role of hepatectomy for non-colorectal liver metastasis (NCLM) is less clear.Patients and methodFrom 2004 to 2017, 264 patients received curative hepatectomy for NCLM (n = 28) and CLM (n = 236). Propensity score (PS) matching was performed between two groups, with respect to the significant confounding factors. Short-term and long-term outcomes were compared between PS matched groups. Univariate analysis was performed to identify prognostic factors affecting overall and recurrence-free survival.ResultsAfter PS matching, there were 28 patients in NCLM group and 56 patients in CLM group. With a median follow-up of 34 months, there was no significant difference in 5-year overall survival rate between NCLM and CLM groups (62% vs. 39%) (P = 0.370). The 5-year recurrence-free survival rate was also comparable between NCLM and CLM groups (23% vs. 22%) (P = 0.707). Use of pre-operative systemic therapy (hazard ratio: 2.335, CI 1.157–4.712), multifocal tumors (hazard ratio: 1.777, CI 1.010–3.127), tumor size (hazard ratio: 1.135, CI 1.012–1.273), R1 resection (hazard ratio: 2.484, CI 1.194–5.169) and severe complications (hazard ratio: 6.507, CI 1.454–29.124), but not tumor type (NCLM vs. CLM), were associated with poor overall survival.ConclusionHepatectomy for NCLM can achieve similar oncological outcomes in selected patients as those with CLM. Significant prognostic factors were identified associating with worse overall survival.     

Neutrophil-to-lymphocyte ratio predicts progression and recurrence of non–muscle-invasive bladder cancer

ObjectiveNeutrophil-to-lymphocyte ratio (NLR) predicts advanced stage disease and decreased survival in patients undergoing radical cystectomy for urothelial carcinoma of the bladder. The predictive value of NLR in non–muscle-invasive bladder cancer (NMIBC) has not been well studied. We aimed to evaluate whether NLR predicted disease recurrence and progression in NMIBC.Materials and methodsThe medical records of 122 consecutive, newly diagnosed, patients with NMIBC treated with transurethral tumor resection, between the years 2003 and 2010, were reviewed. Patients with hematological malignancies (n = 4) and without preoperative NLR (n = 11) were excluded. Cutoff points for NLR were tested separately for recurrence and progression using the standardized cutoff-finder algorithm. Univariate and multivariate Cox regression analyses were used to evaluate the association between NLR and disease recurrence and progression.ResultsThe study cohort comprised 91 men and 16 women at a median age of 68 years. The median NLR was 2.85 (interquartile range: 2–3.9). In total, 68 patients (64%) had an NLR>2.41. Patients with NLR>2.41 were more often men (P = 0.02) and had T1 category tumors (P = 0.034). Analyzed as a continuous variable, higher NLR showed a weak positive association with high tumor grade (R = 0.21, P = 0.028).The median follow-up for patients without disease recurrence was 40 months (interquartile range: 23–51). The estimated 3-year progression-free survival rate in patients with an NLR>2.41 was 61%, compared with 84% in patients with an NLR≤2.41 (P = 0.004). On multivariate analysis, an NLR>2.41 (hazard ratio [HR] = 3.52; 95% CI: 1.33–9.33; P = 0.012) and high-risk tumors compared with low-intermediate-risk tumors (HR = 4.83; 95% CI: 1.31–17.77; P = 0.018), as defined by the European Organization for Research and Treatment of Cancer risk tables, were associated with disease progression. An NLR>2.43 (HR = 1.75; 95% CI: 1.05–2.92; P = 0.032) and treatment with intravesical instillations (HR = 0.49; 95% CI: 0.28–0.85; P = 0.011) were associated with disease recurrence on multivariate analysis.ConclusionsNLR is an independent predictor of disease progression and recurrence in patients with NMIBC without hematological malignancies. Prospective studies are required to validate the role of NLR as a prognostic marker in NMIBC.     

Prognostic Relevance of Lymph Node Ratio and Number of Resected Nodes after Curative Resection of Ampulla of Vater Carcinoma

Background  Nodal metastasis is considered a major prognostic factor in patients with ampulla of Vater carcinoma (AVC). No study has investigated the significance of the ratio between metastatic and resected/examined lymph nodes (LNR) in patients with AVC. Methods  Demographic, operative, and pathology data, including number of resected/evaluated nodes and LNR, were collected from patients who underwent pancreaticoduodenectomy with radical intent for invasive AVC from 1990 to 2005. Survival rates and recurrence patterns were evaluated and predictors were identified. Results  In 90 evaluable patients (51 males, 39 females, median age 62.5 years), 5-year disease-specific survival (DSS) was 61%. The median number of resected/evaluated nodes was 16 (range: 5–47); 50% of the patients had nodal metastases. The 5-year DSS according to LNR was 75%, 49%, 38%, and 0% for LNR = 0, LNR >0 and ≤0.2, LNR >0.2, and ≤0.4, and LNR >0.4 (P = 0.002), respectively. The 5-year DSS was 81% in patients with >16 resected/evaluated nodes compared with 45% in those with ≤16 resected/evaluated nodes (P = 0.001). On multivariate analysis LNR and a number of resected/evaluated nodes >16 were significant predictors of survival; a number of resected/evaluated nodes >16 was also the only independent predictor of recurrence. Conclusions  After curative resection for AVC, LNR and a cutoff of 16 resected/evaluated nodes are powerful prognostic factors. LNR might represent a major parameter for patient stratification in adjuvant treatment trials.     

Neutrophil to lymphocyte ratio changes predict small hepatocellular carcinoma survival

Background

There is limited information available concerning the delta neutrophil to lymphocyte ratio (ΔNLR) in hepatocellular carcinoma (HCC). The present study was designed to evaluate the predictive value of dynamic change of NLR in patients who undergo curative resection for small HCC.

Methods

A retrospective cohort study was performed to analyze 189 patients with small HCC who underwent curative resection between February 2007 and March 2012. Patient data were retrieved from our prospectively maintained database. Patients were divided into two groups: group A (NLR increased, n = 80) and group B (NLR decreased, n = 109). Demographic and clinical data, overall survival (OS), and recurrence-free survival (RFS) were statistically compared and a multivariate analysis was used to identify prognostic factors.

Results

The 1, 3, and 5-y OS in group A was 92.7, 70.0, and 53.0%, respectively, and 96.2, 87.5, and 75.9%, respectively, for group B (P = 0.003); The corresponding 1, 3, and 5-y RFS was 58.7, 37.9, 21.8, and 81.2%, 58.5% and 53.8% for groups A and B, respectively (P <0.001). Multivariate analysis suggested that ΔNLR was an independent prognostic factor for both OS (P = 0.004, Hazard Ratio (HR) = 2.637, 95% confidence interval (CI) 1.356–5.128) and RFS (P <0.001, HR = 2.372, 95% CI 1.563–3.601).

Conclusions

Increased NLR, but not high preoperative NLR or postoperative NLR, helps to predict worse OS and RFS in patients with small HCC who underwent curative resection.     

Surrogate Markers of Resectability in Patients Undergoing Exploration of Potentially Resectable Pancreatic Adenocarcinoma

Despite extensive preoperative staging, a significant number of pancreatic cancers are unresectable at surgical exploration. Patients undergoing pancreatic exploration with a view to resection were studied and comparisons are then made between those undergoing resection and a bypass procedure to identify surrogate markers of unresectability. One hundred thirteen consecutive patients underwent pancreatic exploration for head-of-pancreas (HOP) adenocarcinoma with curative intent. Fifty-five underwent pancreaticoduodenectomy and 58 underwent a bypass procedure. Student’s t test, receiver operator characteristics (ROC) and logistic regression were used to compare the predictive value of preoperative patient variables collected retrospectively. The bypass group had a significantly higher median CA19.9 than the resection group (P = 0.003). Platelet count and neutrophil–lymphocyte ratio (NLR) were also significantly different (P = 0.013 and P = 0.026, respectively). ROC analysis indicated that age ≤65, platelet count >297 × 10⁹/l, CA19.9 ≤473 Ku/l, and CA19.9–bilirubin ratio were predictive variables for resectable disease. NLR and CA19.9–bilirubin ratio had specificity values of 92.9 and 97.0%, respectively. From logistic regression, a raised CA19.9 was found to be an independent risk factor for unresectable disease (P = 0.031). A significant proportion of patients with HOP adenocarcinoma are understaged preoperatively. Preoperative serology including platelet count, NLR, CA19.9, and CA19.9–bilirubin ratio may be used as additional discriminators of resectability particularly for high-risk patients.     

Results of Preoperative Hepatic Arterial Infusion Chemotherapy in Patients Undergoing Liver Resection for Colorectal Liver Metastases

Background Although hepatic artery infusion chemotherapy (HAIC) of floxuridine (FUDR) for colorectal liver metastases (CLM) can produce high response rates, data concerning preoperative HAIC are scarce. The aim of this study was to assess the feasibility and results of liver resection after preoperative HAIC with FUDR. Methods Between 1995 and 2004, 239 patients with isolated CLM received HAIC in our institution. Fifty of these patients underwent subsequent curative liver resection (HAIC group). Short- and long-term results of the HAIC group were compared with the outcomes of 50 patients who underwent liver resection for CLM without preoperative chemotherapy. Results Postoperative morbidity rate were comparable between the two groups. Overall disease-free survival at 1 and 3 years after hepatectomy were 77.5% and 57.5% in the HAIC group and 62.9% and 37% in the control group (P = .036). Overall survival from diagnosis of CLM at 1, 3, and 5 years were 97%, 59%, and 49% in the HAIC group versus 94%, 48%, and 35% in the control group (P = .097). When patients were stratified according to clinical-risk scoring (CRS) system, patients with more advanced disease at the time of liver resection (CRS ≥3) had a median survival of 41 months in the HAIC group (n = 37) and 35 months in the control group (n = 34) (P = .031). Conclusions HAIC of FUDR does not negatively affect the outcome of subsequent liver resection. Preoperative HAIC of FUDR may reduce liver recurrence rate and improve long-term survival in patients with more advanced liver disease. Part of this article was presented at the International Hepato-Pancreato-Biliary Association, 7th World Congress in Edinburgh, Scotland, September 3–7, 2006.     

Surgical Factors Influence the Outcome After Ivor-Lewis Esophagectomy with Intrathoracic Anastomosis for Adenocarcinoma of the Esophagogastric Junction: A Consecutive Series of 240 Patients at an Experienced Center

Background  Despite a considerable number of randomized studies, the surgical approach to locally advanced adenocarcinoma of the esophagogastric junction (AEG) I and II is still discussed controversially. Thus, we evaluated the surgical risk and outcome after an abdominothoracic esophagectomy (Ivor-Lewis) with intrathoracic anastomosis as standard procedure. Methods  Between 1998 and 2006, a total of 240 consecutive patients underwent standardized right thoracoabdominal esophagectomy with two-field lymphadenectomy and intrathoracic anastomosis (Ivor-Lewis operation) for AEG I (n = 206) or AEG II (n = 34). A total of 157 patients (65.4%) had neoadjuvant chemotherapy. Results  Postoperative morbidity occurred in 17.9% (43 of 240). Overall mortality was 3.8% (9 of 240). The majority of patients (4 of 9) died because of severe pulmonary complications (44.4%) irrespective of surgical complications. Neoadjuvant chemotherapy did not increase morbidity or mortality. The median overall survival was 51 months. Multivariate analysis including age >75 years, clinical response to chemotherapy, complications, R-category and N-category revealed R-category (P = .005; relative risk [RR] 0.32, 95% confidence interval [95% CI] 0.14–0.70) and complications (P < .001, RR 0.16, 95% CI 0.08–0.35) as independent prognostic factors for all patients. Complications was the only independent prognostic factor (P < .001, RR 0.09, 95% CI 0.08–0.35) for the R0 resected patients. Conclusions  At an experienced center, Ivor-Lewis resection is a safe surgical procedure. Outcome of patients was significantly influenced by surgical factors such as complete resection and complications. Neoadjuvant chemotherapy did not lead to higher morbidity and mortality. The high mortality from non-surgery–related complications emphasizes the importance of careful preoperative evaluation of comorbidities and patient selection.     

Prognostic Factors and Adjuvant Chemoradiation Therapy After Pancreaticoduodenectomy for Pancreatic Adenocarcinoma

Background  The aim of this study was to determine prognostic factors for survival after resection of pancreatic adenocarcinoma (PC) and to compare outcomes after surgery alone versus surgery plus adjuvant therapy. Methods  We performed a retrospective review of 219 patients who underwent pancreaticoduodenectomy for PC with curative intent between 1995 and 2007. Data were collected prospectively. Postoperative adjuvant chemoradiation therapy (CRT) consisted of fluorouracil or gemcitabine-based chemotherapy; the median radiation dose was 45 Gy. Results  The 3- and 5-year overall survival (OS) rates were 24.3% and 14.2%, respectively. Median OS was 14.0 months [95% confidence interval (CI), 12–16 months]. Patients with metastatic lymph nodes experienced improved median survival (16 vs 10 months; P < 0.001) and 3-year OS (3-year OS 28% vs 8%) after adjuvant CRT compared with those who had no CRT. Patients who underwent non-curative resection had the same effect (median OS, 13 vs 8 months; P = 0.037). Lymph node metastasis and non-curative resection showed no significance on multivariate analysis. Poor differentiation [risk ratio (RR) = 2.10; P < 0.001] and tumor size >3 cm (RR = 1.57; P = 0.018) were found to be adverse prognostic factors; adjuvant CRT had borderline significance (RR = 0.70; P = 0.087). Conclusions  Adjuvant CRT benefited a subset of patients with resected PC, particularly those with lymph node metastasis and those undergoing non-curative resection. Multivariate analysis demonstrated that patients with tumors larger than 3 cm and poor differentiation had poor prognosis.     

Outcome of Locally Recurrent and Metastatic Angiosarcoma

Background  Angiosarcoma (AS) is a rare soft tissue sarcoma with an enhanced propensity for local and systemic failure. The outcome of locally recurrent and metastatic AS treated at a single institution was evaluated. Methods  Medical records of AS patients treated for local recurrence and distant metastasis (1993–2008) were retrospectively reviewed. Univariable and multivariable analyses were performed to identify prognosticators. Results  Forty-four patients were treated for locally recurrent AS; the majority (59%) were ≤5 cm; the most common sites were skin (48%) and breast (32%). Thirty-two patients (73%) had surgery; 73% received chemotherapy; radiation was delivered to 41%. Median disease-specific survival (DSS) was 50 months [95% confidence interval (CI): 25.7–73.5 months]. Multivariable analysis identified size >5 cm as the only independent adverse prognosticator of recurrent AS-specific survival [hazard ratio (HR): 3.26, P = 0.04]. Ninety-nine patients were treated for metastatic AS; 73% had multiple metastatic sites; the lung was the most common site (36%). Chemotherapy, mainly doxorubicin- and/or paclitaxel-based regimens, were administered to 95 patients (96%). Radiotherapy was utilized in 25% cases; 16% of patients underwent curative-intent surgery. Median DSS was 10 months (95% CI: 7.9–12 months). Isolated lymph node metastasis versus hematogenic spread was the only statistically significant favorable prognostic factor identified (HR: 0.29, P = 0.01). Conclusion  Locally recurrent AS is often treatable; complete resection can potentially prolong survival. In contrast, metastatic patients have a grave prognosis; however, patients with isolated lymphatic spread and possibly those treated with taxol-based chemotherapeutic regimens have a favorable outcome.     

Survival of Patients with Synchronous and Metachronous Colorectal Liver Metastases—is there a Difference?

Background  The aim of this study was to compare outcomes in patients with synchronous and metachronous colorectal liver metastases, with special emphasis on prognostic determinants. Study design  We analyzed prospectively collected data on 101 patients with synchronous metastases (group A) who were treated surgically during the time period from April 1998 to December 2006 in regard to overall and disease-free survival, impact of chemotherapy, as well as several serum parameters. A group of patients with metachronous colorectal liver metastases (group B) was considered for baseline comparison. Results  Twenty-three patients in group A received only an explorative laparotomy. Surgical treatment included right hepatectomy (n = 7), left hepatectomy (n = 5), right trisectionectomy (n = 10), left trisectionectomy (n = 1), left lateral resection (n = 11), and sectionectomy (n = 44). Thirty-day mortality was 3%. Morbidity was observed in 10% of the patients. One-, 3-, and 5-year overall survival rates for synchronous metastases were 86%, 68%, and 47%, respectively. The corresponding rates for metachronous metastases were 94%, 68%, and 39% (p > 0.05). Disease free survival was 74%, 42%, and 33% in group A versus 84%, 62%, and 13% in group B (p = 0.28). There was no difference in survival between patients receiving neoadjuvant chemotherapy and no chemotherapy (p > 0.05). Out of all serum parameters, carcinoembryonic antigen levels were a negative predictor for overall and disease-free survival only. Conclusions  Patients with synchronous colorectal liver metastases had a similar 5-year overall and disease-free survival, which corresponds to patients with metachronous metastases. The impact of neoadjuvant chemotherapy in patients with synchronous metastases needs to be further clarified.     

Systemic Chemotherapy and Two-Stage Hepatectomy for Extensive Bilateral Colorectal Liver Metastases: Perioperative Safety and Survival

Background Two-stage hepatectomy has been proposed for patients with bilateral colorectal liver metastases (CLM). The aim of this study was to compare the outcome of patients with CLM treated with preoperative chemotherapy followed by one- or two-stage hepatectomy. Methods From a prospective database, 214 consecutive patients who received preoperative systemic chemotherapy (fluoropyrimidine with irinotecan or oxaliplatin) followed by planned one- or two-stage hepatectomy were retrospectively analyzed (1998–2006). In patients undergoing two-stage procedures, minor hepatectomy (wedge or segmental resection[s]) was systematically performed before major (more than three segments), second-stage hepatectomy. Preoperative portal vein embolization (PVE) was performed if indicated. Results One- (group I) and two-stage(group II) hepatectomies were performed in 184 and 21 patients, respectively. Median number of metastases in groups I and II were two (range 1–20) and seven (range 2–20). All patients in group II had bilateral disease vs 39% in group I. Major hepatectomy was performed in all patients in group II and 79% in group I. PVE was performed in 18 group I and 12 group II patients without increase in morbidity. For group I, group II first stage, and group II second stage, respectively, morbidity (24%, 24%, 43%), median hospital stay (7 days, 6 days, 6.5 days) and 30 days postoperative mortality (2%, 0%, 0%) were not significantly different (P = NS). Median follow-up was 25 months; median survival has not been reached. One- and 3-year overall and disease-free survival rates from the time of hepatic resection were 95% and 75%, 63% and 39%, respectively in group I; 95% and 86%, 70% and 51%, respectively in group II (P = NS). Conclusions Two-stage hepatectomy with preoperative chemotherapy results in comparable morbidity and survival rates as one-stage hepatectomy. This approach enables selection and treatment of patients with multiple, bilateral CLM who will benefit from aggressive surgery with good outcomes. Presented at the Society for Surgery of the Alimentary Tract 48th Annual Meeting, May 2007, Washington, DC.     

Major Hepatectomy for Colorectal Metastases: Is Preoperative Portal Occlusion an Oncological Risk Factor?

Background  This study investigates oncological risks and benefits of portal occlusion (PO) in major resection for colorectal liver metastases (CLM). Methods  Between 1995 and 2004, 107 patients were scheduled for major hepatectomy for CLM. Of these, 53 patients were selected for PO due to insufficient future liver remnant (FLR), and 54 patients had straightforward hepatectomy. Associations of clinicopathologic factors with resectability, and outcome after PO were analyzed. Results  21 of 53 patients (39.6%) after PO were unresectable. These patients had a significant smaller volume of the FLR than the 32 resected patients after PO (P = .029). In total, 17 patients (80.9%) did not undergo resection due to cancer progression. Among these, 11 patients (52.4%) exhibited either a progression of known metastases located in the occluded lobes, or new metastases in the nonoccluded portion of the liver. In another 4 individuals (19%), the decision against resection resulted from insufficient hypertrophy of the FLR. Following major hepatectomy, the 5-year survival was 43.66%. Although there was a significantly higher rate of extended hepatectomies versus formal hepatectomies (P < .001), more bilobar distributed metastases versus unilobar manifestations (P = .015), and a smaller resection margin (P = .01) in patients who had PO, no adverse effect on mortality, morbidity, recurrence and survival was observed. Conclusion  Unresectability after PO is a major problem that warrants multidisciplinary improvements, and randomization to resection with or without PO remains ethically problematic. However, following adequate patient selection, PO may provide a significant survival benefit for patients with prior unresectable CLM. L. Mueller and C. Hillert contributed equally to this work.     

Crossing the Rubicon: When Pancreatic Resection with Curative Intent Ends in an R2 Status

Aim  To analyze the impact of pancreatitis-mimicking, concomitant alterations on intraoperative assessment of curative resectability, the anatomical site of irresectability, and outcome after nonintentional R2 resection in pancreatic cancer. Methods  Of 1,099 patients subjected to pancreatic resection for cancer, 40 (4%) underwent R2 resection (group A). The site where tumors turned out to be irresectable and the coincident presence of potentially misleading, fibro-desmoplastic alterations were analyzed. Outcome after resection was compared with 40 bypass patients matched for age, gender, histopathology, and use of additive chemotherapy (group B). Results  R2 resection was due to misjudgment regarding resectability in 38 patients (95%) and to uncontrollable hemorrhage in 2 patients (5%). Group A patients had significantly longer operative times (P < 0.0001), required more blood units (P < 0.0001), and had longer hospital stay than group B patients (P = 0.049). Despite a significantly higher relaparotomy rate of 20% (n = 8) in group A versus 5% (n = 2) in group B, perioperative mortality was equal (n = 2, each). Median survival was 11.5 months in group A and 7.5 months in group B (P = 0.014). “Pancreatitis-like” lesions were assessed in 70% (n = 28/40, group A) and 25% (10/40, group B; P = 0.014). The superior mesenteric artery proximal to its jejunal branches was the most likely site of irresectability (60%), followed by its peripheral course (22.5%) and the lower aspects of the celiac trunk (17.5%). Conclusions  Concomitant “pancreatitis-like” alterations hamper the assessment of local resectability in pancreatic cancer. Although palliative resection results in elevated perioperative morbidity compared with bypass procedures, mortality is equal, while survival is prolonged. Maximilian Bockhorn and Guellue Cataldegirmen contributed equally to this study.     

Complete Soft Tissue Sarcoma Resection is a Viable Treatment Option for Select Elderly Patients

Background  Decreased performance status, comorbidities, and disease natural history may erode enthusiasm for soft tissue sarcoma (STS) resection in elderly patients. Consequently, we evaluated the outcome of elderly patients amenable to complete surgical resection treated at a single institution. Methods  Prospectively accrued data were used to identify patients with primary STS age ≥65 years (n = 325) who underwent complete macroscopic resection at our institution (1996–2007). Univariable and multivariable analyses were performed to identify prognostic factors. Results  Median age at presentation was 72 years; 179 patients (55.1%) had associated comorbidities with an ASA score of ≥3. Extremity was the most common site (57.1%; n = 186), undifferentiated pleomorphic sarcoma the most common histology (60.4%; n = 197); 232 (71.2%) were high grade, 222 (68.3%) were >5 cm. Thirty-day postoperative mortality was 0.9% (n = 3); overall complication rate was 30.7% (n = 100), and mean postoperative hospital stay was 9 days (range, 1–84). Estimated median survival was 96 months, 5-year disease-specific survival (DSS) was 63%. Multivariable analysis identified age ≥75 year (HR = 2.03), tumor size: 5–15 vs <5 cm (HR = 3.54), or >15 vs <5 cm (HR = 10.33), and high-grade (HR = 5.53) as significant independent adverse prognostic factors. Compared with patients aged 65–74 years, older patients had more high grade tumors (P = .04), received chemotherapy less often (P < .0001), developed different patterns of recurrence (P < .05), and exhibited a shorter median survival (70 months; P = .05). Conclusions  Properly selected elderly patients can safely undergo extensive STS resections. Until more effective therapies become available, surgery in the elderly is indicated and remains the best means for STS control.     

Diffuse Malignant Peritoneal Mesothelioma: Failure Analysis Following Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

Improved survival has been reported for diffuse malignant peritoneal mesothelioma (DMPM) treated by cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). The issue of treatment failure has never been extensively addressed. The present study assessed the failure pattern, management, and outcome of progressive DMPM following comprehensive treatment. Clinical data on 70 patients with DMPM undergoing cytoreduction and HIPEC were prospectively collected; after a median follow-up of 43 months, disease progression occurred in 38 patients. Progressive disease distribution in 13 abdominopelvic regions was analyzed. In 28 patients undergoing adequate cytoreduction (residual tumor ≤2.5 mm), clinicopathological factors correlating to disease progression in each region were investigated. Median time to progression was 9 months [95% confidence interval (CI) 1.6–35.9]. Median survival from progression was 8 months (95% CI 4–16.2). The failure pattern was categorized as peritoneal progression (n = 31), liver metastases (n = 1), abdominal lymph-node involvement (n = 2), pleural seeding (n = 4). Small bowel was the single site most commonly involved (n = 27). Residual tumor ≤2.5 mm (versus no visible) was the only independent risk factor for disease progression in epigastric region (P = 0.047), upper ileum (P = 0.029), upper jejunum (P = 0.034), and lower jejunum (P = 0.002). Progressive disease was treated with second HIPEC in 3 patients, debulking in 4, systemic chemotherapy in 16, and supportive care in 15. At multivariate analysis, time to progression <9 months (P = 0.009), poor performance status (P = 0.005), and supportive care (P = 0.003) correlated to reduced survival from progression. We conclude that minimal residual disease, compared with macroscopically complete cytoreduction, correlated to failure in critical anatomical areas, suggesting the need for maximal cytoreductive surgical efforts. In selected patients, aggressive management of progressive disease seems worthwhile.