Akshat Saxena

Should the treatment of peritoneal carcinomatosis by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy still be regarded as a highly morbid procedure? A systematic review of morbidity and mortality

Background:Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been offered in many institutions worldwide since the 1990s. Despite its existence of more than 10 years, this treatment has received heavy criticism for its morbidity and mortality rates. This consequentially resulted in a lack of randomized trials being conducted and translates into a lack of the most reliable form of scientific evidence in clinical research, hence limiting its general acceptance. Objective:To report the morbidity and mortality outcomes of CRS and HIPEC from all institutions performing this treatment as a prelude toward establishing the safety of this treatment for peritoneal carcinomatosis. Methods:A systematic review of relevant studies before August 2008 was performed. Each study was appraised using a predetermined protocol. The quality of studies was assessed. The morbidity and mortality of the treatment were synthesized through a narrative review with full tabulation of results of all included studies. Conclusions:The morbidity and mortality outcomes of CRS and HIPEC are similar to a major gastrointestinal surgery, such as a Whipples procedure. To derive the maximal benefit of this treatment, careful patient selection with an optimal level of postoperative care must be advocated to avoid undesirable complications of this treatment.

A systematic review and meta-analysis on the impact of pre-operative neutrophil lymphocyte ratio on long term outcomes after curative intent resection of solid tumours.

INTRODUCTION There is increasing evidence to suggest that cancer-associated inflammation is associated with poorer long-term outcomes. Various markers have been studied over the past decade in an attempt to improve selection of patients for surgery. This meta-analysis explored the association between the neutrophil-lymphocyte ratio and prognosis following curative-intent surgery for solid tumours. METHODS Studies were identified from US National Library of Medicine (Medline) and the Exerpta Medica database (EBASE) performed in March 2013. A systematic review and meta-analysis were performed to generate combined hazard ratios for overall survival (OS) and disease-free survival (DFS). RESULTS Forty-nine studies containing 14282 patients were included. Elevated NLR was associated with poorer overall survival [HR: 1.92, 95% CI (1.64-2.24)] (p < 0.001) and disease-free survival [HR: 1.99, 95% CI (1.80-2.20)] (p < 0.001). Significant heterogeneity was found with an I(2) of 77% and 97% for OS and DFS respectively. Subgroup analyses demonstrated that gastro-intestinal malignancies; mainly gastric [HR: 1.97, 95% CI (1.41-2.76)], colorectal [HR: 1.65, 95% CI (1.21-2.26)] and oesophageal [HR: 1.48, 95% CI (0.91-2.42)] cancers were predictive of OS (I(2) = 54.3%). A separate analysis for studies using an NLR cutoff of 5 demonstrated significantly poorer outcomes [HR: 2.18, 95% CI (1.74-2.73)] (p = 0.002) with less heterogeneity (I(2) = 58%). CONCLUSION Elevated NLR correlates with poorer prognosis. It potentially represents a simple, robust and reliable measure that may be useful in identifying high-risk groups who could benefit from adjuvant therapy.

Factors predicting response and survival after yttrium-90 radioembolization of unresectable neuroendocrine tumor liver metastases: a critical appraisal of 48 cases.

Background:Yttrium-90 (90Y) radioembolization is a promising treatment option for unresectable neuroendocrine tumor liver metastases (NETLM). This study is the first to evaluate the prognostic variables that influenced radiologic response and survival in patients with unresectable NETLM who were treated with 90Y radioembolization. As a secondary outcome, the impact of this treatment on serologic toxicity was assessed. Methods:Forty-eight patients underwent resin-based 90Y radioembolization for unresectable NETLM at a single institution between December 2003 and May 2009. Patients were assessed radiologically and serologically at 1 month and then at 3 month intervals after treatment. Prognostic variables that affected response and survival were determined. The impact of this treatment on serologic toxicity over a 6-month period was assessed. Discussion:No patient was lost to follow-up. The median follow-up for the patients who were alive was 41 months. The median survival was 35 months (range: 5–63). On imaging follow-up, 7 patients (15%) had a complete response and 19 patients (40%) had a partial response to treatment. Eleven patients (23%) had stable disease and 11 patients (23%) had progressive disease. Five prognostic factors were associated with an improved survival: complete/partial response (P = 0.003), low hepatic tumor burden (P = 0.022), female gender (P = 0.022), well-differentiated tumor (P = 0.001), and absence of extra—hepatic metastasis (P < 0.001). Three factors were associated with a complete/partial response: female gender (P = 0.040), well-differentiated tumor (P < 0.001) and low hepatic tumor burden (P = 0.041). There was a significant increase in the level of alkaline phosphatase over the 6-month period (P < 0.001). Conclusions:90Y radioembolization is a promising treatment option for unresectable NETLM. Patients with low hepatic tumor burden, well-differentiated tumor, female gender, and no extrahepatic disease benefit most from treatment.

Systematic Review of Randomized and Nonrandomized Trials of the Clinical Response and Outcomes of Neoadjuvant Systemic Chemotherapy for Resectable Colorectal Liver Metastases

BackgroundNeoadjuvant chemotherapy prior to hepatectomy in patients with resectable colorectal liver metastases (CLM) may facilitate the resectability of the liver lesions and treat occult metastasis but may also lead to hepatic parenchyma damage. There is argument over the oncologic benefit of this practice in patients who would already be suitable for a curative hepatectomy.MethodsExtensive literature search of databases (MEDLINE and PubMed) to identify published studies of preoperative systemic chemotherapy for resectable CLM was undertaken with clinical response to treatment and survival outcomes as the endpoints.ResultsTwenty-three studies were reviewed: 1 phase III randomized control trial, 3 phase II studies, and 19 observational studies, comprising 3,278 patients. Objective (complete/partial) radiological response was observed in 64% (range 44–100%) [complete 4% (range 0–38%), partial 52% (range 10–90%)] of patients after neoadjuvant chemotherapy. Pathologically, a median of 9% (range 2–24%) and 36% (range 20–60%) had complete and partial response, respectively. Of patients, 41% (range 0–65%) had stable or progressive disease whilst on neoadjuvant chemotherapy. Median disease-free survival (DFS) was 21 (range 11–40) months. Median overall survival (OS) was 46 (range 20–67) months.ConclusionCurrent evidence suggests that objective response to neoadjuvant chemotherapy may be achieved with improvement in DFS in patients with resectable CLM. A prospective randomized trial of neoadjuvant therapy versus adjuvant therapy after liver resection is required to determine the optimal perisurgical treatment regimen.Neoadjuvant chemotherapy prior to hepatectomy in patients with resectable colorectal liver metastases (CLM) may facilitate the resectability of the liver lesions and treat occult metastasis but may also lead to hepatic parenchyma damage. There is argument over the oncologic benefit of this practice in patients who would already be suitable for a curative hepatectomy. Extensive literature search of databases (MEDLINE and PubMed) to identify published studies of preoperative systemic chemotherapy for resectable CLM was undertaken with clinical response to treatment and survival outcomes as the endpoints. Twenty-three studies were reviewed: 1 phase III randomized control trial, 3 phase II studies, and 19 observational studies, comprising 3,278 patients. Objective (complete/partial) radiological response was observed in 64% (range 44–100%) [complete 4% (range 0–38%), partial 52% (range 10–90%)] of patients after neoadjuvant chemotherapy. Pathologically, a median of 9% (range 2–24%) and 36% (range 20–60%) had complete and partial response, respectively. Of patients, 41% (range 0–65%) had stable or progressive disease whilst on neoadjuvant chemotherapy. Median disease-free survival (DFS) was 21 (range 11–40) months. Median overall survival (OS) was 46 (range 20–67) months. Current evidence suggests that objective response to neoadjuvant chemotherapy may be achieved with improvement in DFS in patients with resectable CLM. A prospective randomized trial of neoadjuvant therapy versus adjuvant therapy after liver resection is required to determine the optimal perisurgical treatment regimen.

Radioembolization versus Standard Care of Hepatic Metastases: Comparative Retrospective Cohort Study of Survival Outcomes and Adverse Events in Salvage Patients

PURPOSE To retrospectively evaluate the safety and survival of patients with chemotherapy-refractory liver metastases treated with yttrium-90 ((90)Y) resin microspheres, and to compare survival in this patient group versus survival after standard/supportive care to assess whether radioembolization contributes to survival gains in the salvage setting. MATERIALS AND METHODS While 339 patients with chemotherapy-refractory liver metastases underwent (90)Y microspheres radioembolization at a single institution between 2006 and 2011, 51 patients were referred back to their treating physician for conservative treatment or best supportive care. Adverse events were assessed at the time of treatment and at 1 and 3 months after treatment. Overall survival (OS) was calculated by the Kaplan-Meier method for the radioembolization cohort (as a whole and according to two subcohorts: patients with colorectal primary cancer and patients with all other primary cancers, eg, breast or neuroendocrine) and the standard-care cohort. RESULTS The median OS after (90)Y radioembolization (339 patients) was 12.0 months, versus 6.3 months for the standard-care cohort (51 patients; P < .001). The median OS times for the two subcohorts were 11.9 months and 12.7 months, respectively. At the 3-month follow-up, the incidence of more serious adverse events was low, with 11 cases (3%) of ulceration, 10 cases (2.9%) of radiation-induced liver disease, and six complications (1.8%) involving the gallbladder (eg, cholecystitis). CONCLUSIONS The present study suggests that radioembolization shows promise as an effective and safe treatment for patients with chemotherapy-refractory hepatic metastases and improves overall survival in a select population of patients in a salvage setting compared with best supportive care alone.

Usefulness of postoperative atrial fibrillation as an independent predictor for worse early and late outcomes after isolated coronary artery bypass grafting (multicenter Australian study of 19,497 patients).

Several studies have shown that postoperative atrial fibrillation (POAF) is associated with poorer short- and long-term outcomes after isolated coronary artery bypass grafting surgery. Nevertheless, there is considerable debate as to whether this reflects an independent association of POAF with poorer outcomes or confounding by other factors. We sought to investigate this issue. Data obtained from June 2001 through December 2009 by the Australasian Society of Cardiac and Thoracic Surgeons National Cardiac Surgery Database Program were retrospectively analyzed. Demographic and operative data were compared between patients who developed POAF and those who did not using chi-square and t tests. The independent impact of POAF on 14 short-term complications and long-term mortality was determined using binary logistic and Cox regression, respectively. Excluding patients with preoperative arrhythmia, isolated coronary artery bypass grafting surgery was performed in 19,497 patients. Of these, 5,547 (28.5%) developed POAF. Patients with POAF were generally older (mean age 69 vs 65 years, p <0.001) and presented more often with co-morbidities including congestive heart failure (p <0.001), hypertension (p <0.001), cerebrovascular disease (p <0.001), and renal failure (p = 0.046). Patients with POAF demonstrated a greater 30-day mortality on univariate analysis but not on multivariate analysis (p = 0.376). Patients with POAF were, however, at an independently increased risk of perioperative complications including permanent stroke (p <0.001), new renal failure (p <0.001), infective complications (p <0.001), gastrointestinal complications (p <0.001), and return to the theater (p <0.001). POAF was also independently associated with shorter long-term survival (p = 0.002). In conclusion, POAF is a risk factor for short-term morbidity and decreased long-term survival. Rigorous evaluation of various therapies that prevent or decrease the impact of POAF is imperative. Moreover, patients who develop POAF should undergo strict surveillance and be routinely screened for complications after discharge.

Hepatic resection for metastatic breast cancer: A systematic review

BACKGROUND Systemic chemotherapy is the mainstay of treatment for metastatic breast cancer with the role of surgery being strictly limited for palliation of metastatic complications or locoregional relapse. An increasing number of studies examining the role of therapeutic hepatic metastasectomy show encouraging survival results. A systematic review was undertaken to define its safety, efficacy and to identify prognostic factors associated with survival. METHODS Electronic search of the MEDLINE and PubMed databases (January 2000-January 2011) to identify studies reporting outcomes of hepatectomy for breast cancer liver metastases (BCLM) with hepatectomy was undertaken. Two reviewers independently appraised each study using a predetermined protocol. Safety and clinical efficacy was synthesised through a narrative review with full tabulation of results of all included studies. RESULTS Nineteen studies were examined. This comprised of 553 patients. Hepatectomy for BCLM was performed at a rate of 1.8 (range, 0.7-7.7) cases per year in reported series. The median time to liver metastases occurred at a median of 40 (range, 23-77) months. The median mortality and complication rate were 0% (range, 0-6%) and 21% (range, 0-44%), respectively. The median overall survival was 40 (range, 15-74) months and median 5-year survival rate was 40% (range, 21-80%). Potential prognostic factors associated with a poorer overall survival include a positive liver surgical margin and hormone refractory disease. CONCLUSION Hepatectomy is rarely performed for BCLM but the studies described in this review indicate consistent results with superior 5-year survival for selected patients with isolated liver metastases and in those with well controlled minimal extrahepatic disease. To evaluate its efficacy and control for selection bias, a randomised trial of standard chemotherapy with or without hepatectomy for BCLM is warranted.

Sex differences in outcomes following isolated coronary artery bypass graft surgery in Australian patients: analysis of the Australasian Society of Cardiac and Thoracic Surgeons cardiac surgery database

OBJECTIVES Women undergoing isolated coronary artery bypass graft (CABG) surgery have been previously shown to be at an independently increased risk for post-operative morbidity and mortality. The current study evaluates the impact of sex as an independent risk factor for early and late morbidity and mortality following isolated CABG surgery. METHODS Data obtained between June 2001 and December 2009 by the Australasian Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database Program was retrospectively analysed. Demographic, operative data and post-operative complications were compared between male and female patients using chi-square and t-tests. Long-term survival analysis was performed using Kaplan-Meier survival curves and the log-rank test. Independent risk factors for short- and long-term mortality were identified using binary logistic and Cox regression, respectively. RESULTS CABG surgery was undertaken in 21 534 patients at 18 Australian institutions; 22.2% were female. Female patients were generally older (mean age, 68 vs. 65 years, P < 0.001) and presented more often with congestive heart failure (P < 0.001), hypertension (P < 0.001), diabetes mellitus (P < 0.001) and cerebrovascular disease (P < 0.001). Women demonstrated a greater 30-day mortality (2.2% vs. 1.5%, P < 0.001) on univariate analysis but not on multivariate analysis (P = 0.638). Similarly, women demonstrated a greater late mortality than men on univariate analysis (P = 0.006) but not on multivariate analysis (P = 0.093). Women had a decreased risk of early complications including new renal failure (P = 0.001) and deep sternal wound infection (P = 0.017) but were more likely to require red blood cell transfusion (P < 0.001). CONCLUSIONS Female patients undergoing isolated CABG surgery have a greater 30-day mortality which may be accounted for by a poorer pre-operative risk factor profile. Further investigation is required into the reasons for differential outcome after CABG based on sex.

Long-term outcome of image-guided percutaneous radiofrequency ablation of lung metastases: an open-labeled prospective trial of 148 patients

BACKGROUND Image-guided percutaneous radiofrequency ablation (RFA) has been proposed as an efficacious local therapy for lung metastases in nonsurgical candidates. Reports of long-term outcome from this treatment have been limited. METHODS A prospective open-labeled trial of RFA was initiated in November 2000 for treatment of lung metastases in nonsurgical candidates. RFA was carried out under fluoroscopic computed tomography. Treatment complications and survival parameters were analyzed. RESULTS Of 148 patients treated, 66 patients (46%) had a complete response, 38 patents (26%) had a partial response, 57 patients (39%) had stable disease and 23 patients (16%) had progressive disease. The median progression-free survival was 11 months [95% confidence interval (CI) 9-14]. The median overall survival and 3- and 5-year survivals were 51 months (95% CI 19-83) and 60% and 45%, respectively. Disease-free interval (P = 0.013) and response to treatment (P = 0.002) were independent predictors for overall survival. Complications occurred in up to 45% of patients, of which 45 patients (30%) required chest tube placement. CONCLUSION This analysis confirms that RFA of lung metastases may achieve long-term survival in nonsurgical candidates with an acceptable complication rate hence supporting its incorporation into the oncosurgical management of lung metastases for the purposes of cure, stabilization and disease prolongation.

Systematic review of neoadjuvant transarterial chemoembolization for resectable hepatocellular carcinoma.

Resection of hepatocellular carcinoma (HCC) offers the only hope for cure. However, in patients undergoing resection, recurrences, in particular, intrahepatic recurrence are common. The effectiveness of transarterial chemoembolization (TACE) as a neoadjuvant therapy for unresectable HCC was exploited by numerous liver units and employed preoperatively in the setting of resectable HCC with an aim to prevent recurrence and prolong survival. A systematic literature search of databases (Medline and PubMed) to identify published studies of TACE administered preoperatively as a neoadjuvant treatment for resectable HCC was undertaken. A systematic review by tabulation of the results was performed with disease‐free survival (DFS) as the primary endpoint. Overall survival (OS), rate of pathological response, impact on surgical morbidity and mortality and pattern of recurrences were secondary endpoints of this review. Eighteen studies; three randomized trials and 15 observational studies were evaluated. This comprised of 3927 patients, of which, 1293 underwent neoadjuvant TACE. The median DFS in the TACE and non‐TACE group ranged from 10 to 46 and 8 to 52 months, respectively, with 67% of studies reporting similar DFS between groups despite higher extent of tumour necrosis from the resected specimens indicating a higher rate of pathological response (partial TACE 27–72% vs. non‐TACE 23–52%; complete TACE 0–28% vs. non‐TACE zero), with no difference in surgical morbidity and mortality outcome. No conclusion could be drawn with respect to OS. Both randomized and non‐randomized trials suggest the use of TACE preoperatively as a neoadjuvant treatment in resectable HCC is a safe and efficacious procedure with high rates of pathological responses. However, it does not appear to improve DFS.