Surgical debulking is associated with improved survival for patients with neuroendocrine liver metastases of unknown primary.

BACKGROUND: Resection of neuroendocrine tumors (NET) with surgical debulking of liver metastasis (NETLM) is associated with improved survival. In patients with an unknown primary (UP-NETLM), the effects of debulking remains unclear. METHODS: The National Cancer Database (2004-2016) was queried for patients with small intestine (SI) and pancreas (P) NETLMs. If the liver was listed as the primary site, the patient's disease was classified as UP-NETLM. RESULTS: Patients with UP-NETLM, SI-NETLM, and P-NETLM who were managed non-operatively demonstrated a significant difference in 5-year overall survival (OS) (21.5% vs. 39.2% vs. 17.1%; p < 0.0001). OS in patients who underwent debulking was higher (63.7% vs. 73.2% vs. 54.2%). Patients with UP-NETLMs who underwent debulking had similar OS to patient with SI-NETLM (p = 0.051), but significantly higher OS, depending on tumor differentiation, compared to patients with P-NETLMs. If well-differentiated, surgery for UP-NETLMs was associated with a higher rate of OS (p = 0.009), while no difference was observed if moderately (p = 0.209) or poorly/undifferentiated (p = 0.633). P-NETLMs were associated with worse OS (p < 0.001) on multivariate analysis. DISCUSSION: Debulking in patients with UP-NETLMs was associated with similar OS compared to patients with SI-NETLMs and better or similar OS compared to patient with P-NETLMs.

Preoperative radiation as part of a multidisciplinary strategy for a medically inoperable patient with a bleeding colon cancer.

An 84-year-old man with a history of deep vein thrombosis on warfarin and coronary artery disease presented with haematochezia and was diagnosed with an ascending colon cancer. He was short of breath with lower extremity oedema at the initial surgical consultation. Evaluation revealed an acute exacerbation of congestive heart failure, and further workup and treatment were recommended by the cardiology team. After multidisciplinary discussion, he underwent radiation for the control of bleeding, followed by cardiac catheterisation and placement of a bare metal stent. The patient subsequently underwent robotic-assisted right hemicolectomy. Pathology demonstrated a complete response, and the patient recovered uneventfully. He is alive swith no evidence of disease recurrence 12 months after surgery and 18 months after initial diagnosis.

Bone Pain and Muscle Weakness in Cancer Patients.

PURPOSE OF REVIEW: In this article, we will discuss the current understanding of bone pain and muscle weakness in cancer patients. We will describe the underlying physiology and mechanisms of cancer-induced bone pain (CIBP) and cancer-induced muscle wasting (CIMW), as well as current methods of diagnosis and treatment. We will discuss future therapies and research directions to help patients with these problems. RECENT FINDINGS: There are several pharmacologic therapies that are currently in preclinical and clinical testing that appear to be promising adjuncts to current CIBP and CIMW therapies. Such therapies include resiniferitoxin, which is a targeted inhibitor of noceciptive nerve fibers, and selective androgen receptor modulators, which show promise in increasing lean mass. CIBP and CIMW are significant causes of morbidity in affected patients. Current management is mostly palliative; however, targeted therapies are poised to revolutionize how these problems are treated.

Value of primary operative drain placement after major hepatectomy: a multi-institutional analysis of 1,041 patients.

BACKGROUND: The value of routine primary (intraoperative) drain placement after major hepatectomy remains unclear. We sought to determine if primary drainage led to decreased rates of complications, specifically, intra-abdominal biloma or infection requiring a secondary (postoperative) drainage procedure. STUDY DESIGN: All patients who underwent major hepatectomy (≥3 hepatic segments) at 3 institutions, from 2000 to 2012, were identified. Patients with biliary anastomoses were excluded. Primary outcomes were any complication, rate of secondary drainage procedures, bile leak, and 30-day readmission. RESULTS: There were 1,041 patients who underwent major hepatectomy without biliary anastomosis; 564 (54%) had primary drains placed at the surgeon's discretion. Primary drain placement was associated with increased complications (56% vs 44%; p < 0.001), bile leaks (7.3% vs 4.2%; p = 0.048), and 30-day readmissions (16.4% vs 8.0%; p < 0.001), but was not associated with a decrease in secondary drainage procedures (8.0% vs 5.9%; p = 0.23). Patients with primary drains demonstrated higher American Society of Anesthesioloigsts (ASA) class, greater blood loss, more transfusions, and larger resections. After accounting for these significant clinicopathologic variables on multivariate analysis, primary drain placement was not associated with increased risk of any complications. Primary drainage was, however, independently associated with increased risk of bile leak (hazard ratio [HR] 2.04; 95% CI1.02 to 4.09; p = 0.044) and 30-day readmission (HR 1.79; 95% CI1.14 to 2.80; p = 0.011). There still was no reduction in the need for secondary drainage procedures (HR 0.98; p = 0.96). CONCLUSIONS: Primary intraoperative drain placement after major hepatectomy does not decrease the need for secondary drainage procedures and may be associated with increased bile leaks and 30-day readmissions. Routine drain placement is not warranted.

The effect of preoperative renal insufficiency on postoperative outcomes after major hepatectomy: a multi-institutional analysis of 1,170 patients.

BACKGROUND: Renal insufficiency adversely affects outcomes after cardiac and vascular surgery. The effect of preoperative renal insufficiency on outcomes after major hepatectomy is unknown. STUDY DESIGN: All patients who underwent major hepatectomy (≥3 segments) at 3 institutions from 2000 to 2012 were identified. Resections were performed using low central venous pressure anesthesia. Renal function was analyzed by preoperative serum creatinine (sCr) level. Primary outcomes were major complications (Clavien grade III to V), respiratory failure, renal failure requiring hemodialysis, and 90-day mortality. RESULTS: One thousand one hundred and seventy patients had preoperative sCr levels available. Renal function was analyzed using sCr dichotomized at 1.8 mg/dL, 1 SD higher than the mean value (0.97 ± 0.79 mg/dL) for the cohort. Twenty-two patients had sCr ≥1.8 mg/dL. Major complications occurred in 279 patients (23.8%), respiratory failure in 62 (5.3%), and renal failure in 31 (2.6%). Ninety-day mortality rate was 5.4%. On multivariate analysis, patients with sCr ≥1.8 mg/dL remained at significantly increased risk for major complications (hazard ratio = 3.94; 95% CI, 1.48-10.49; p = 0.006), respiratory failure (hazard ratio = 4.43; 95% CI, 1.33-14.80; p = 0.014), and renal failure (hazard ratio = 4.75; 95% CI, 1.19-18.97; p = 0.028). Serum Cr ≥1.8 mg/dL was not independently associated with 90-day mortality on multivariate analysis (p = 0.27). CONCLUSIONS: Preoperative serum creatinine ≥1.8 mg/dL identifies patients at significantly increased risk of postoperative major complications, respiratory failure, and renal failure requiring dialysis. Patients are well selected for major hepatectomy, and few patients with substantial renal insufficiency are deemed operative candidates.

Value of intraoperative neck margin analysis during Whipple for pancreatic adenocarcinoma: a multicenter analysis of 1399 patients.

INTRODUCTION: During pancreaticoduodenectomy (PD) for ductal adenocarcinoma, a frozen section (FS) neck margin is typically assessed, and if positive, additional pancreas is removed to achieve an R0 margin. We analyzed the association of this practice with improved overall survival (OS). METHODS: Patients who underwent PD for pancreatic ductal adenocarcinoma from January 2000 to August 2012 at 8 academic centers were classified by neck margin status as negative (R0) or microscopically positive (R1) on the basis of FS and permanent section (PS). Impact on OS of converting an FS-R1-neck margin to a PS-R0-neck margin by additional resection was assessed. RESULTS: A total of 1399 patients had FS neck margins analyzed. Median OS was 19.7 months. On FS, 152 patients (10.9%) were R1, and an additional 51 patients (3.6%) had false-negative FS-R0 margins. PS-R0-neck was achieved in 1196 patients (85.5%), 131 patients (9.3%) remained PS-R1, and 72 patients (5.1%) were converted from FS-R1-to-PS-R0 by additional resection. Median OS for PS-R0-neck patients was 21.1 months versus 13.7 months for PS-R1-neck patients (P < 0.001) and 11.9 months for FS-R1-to-PS-R0 patients (P < 0.001). Both FS-R1-to-PS-R0 and PS-R1-neck patients had larger tumors (P = 0.001), more perineural invasion (P = 0.02), and more node positivity (P = 0.08) than PS-R0-neck patients. On multivariate analysis controlling for adverse pathologic factors, FS-R1-to-PS-R0 conversion remained associated with significantly worse OS compared with PS-R0-neck patients (hazard ratio: 1.55; P = 0.009). CONCLUSIONS: For patients who undergo pancreaticoduodenectomy for pancreatic ductal adenocarcinoma, additional resection to achieve a negative neck margin after positive frozen section is not associated with improved OS.

Hypophosphataemia after major hepatectomy and the risk of post-operative hepatic insufficiency and mortality: an analysis of 719 patients.

BACKGROUND: Hypophosphataemia after a hepatectomy suggests hepatic regeneration. It was hypothesized that the absence of hypophosphataemia is associated with post-operative hepatic insufficiency (PHI) and complications. METHODS: Patients who underwent a major hepatectomy from 2000-2012 at a single institution were identified. Post-operative serum phosphorus levels were assessed. Primary outcomes were PHI (peak bilirubin >7 mg/dl), major complications, and 30- and 90-day mortality. RESULTS: Seven hundred and nineteen out of 749 patients had post-operative phosphorus levels available. PHI and major complications occurred in 63 (8.8%) and 169 (23.5%) patients, respectively. Thirty- and 90-day mortality were 4.0% and 5.4%, respectively. The median phosphorus level on post-operative-day (POD) 2 was 2.2 mg/dl; 231 patients (32.1%) had phosphorus >2.4 on POD2. Patients with POD2 phosphorus >2.4 had a significantly higher incidence of PHI, major complications and mortality. On multivariate analysis, POD2 phosphorus >2.4 remained a significant risk factor for PHI [(hazard ratio HR):1.78; 95% confidence interval (CI):1.02-3.17; P = 0.048], major complications (HR:1.57; 95%CI:1.02-2.47; P = 0.049), 30-day mortality (HR:2.70; 95%CI:1.08-6.76; P = 0.034) and 90-day mortality (HR:2.51; 95%CI:1.03-6.15; P = 0.044). Similarly, patients whose phosphorus level reached nadir after POD3 had higher PHI, major complications and mortality. CONCLUSION: Elevated POD2 phosphorus levels >2.4 mg/dl and a delayed nadir in phosphorus beyond POD3 are associated with increased post-operative hepatic insufficiency, major complications and early mortality. Failure to develop hypophosphataemia within 72 h after a major hepatectomy may reflect insufficient liver remnant regeneration.

Effect of preoperative renal insufficiency on postoperative outcomes after pancreatic resection: a single institution experience of 1,061 consecutive patients.

BACKGROUND: Chronic kidney disease (CKD) is known to adversely affect cardiac and vascular surgery outcomes. We examined the effect of preoperative renal insufficiency on postoperative outcomes after pancreatic resection. STUDY DESIGN: All patients who underwent pancreatic resection between January 2005 and July 2012 were identified. Glomerular filtration rate (eGFR) was estimated by the Modification of Diet in Renal Disease formula. Severe CKD (stages 4-5) was defined as eGFR < 30 mL/min/1.73 m(2). Renal function also was analyzed using serum creatinine (sCr) dichotomized at 1.8 mg/dL. Primary outcomes were any complication, major complications, and respiratory failure. Multivariate models for each endpoint were constructed by including all variables with p value ≤ 0.10 on univariate analysis. RESULTS: There were 1,061 patients identified; 709 underwent pancreaticoduodenectomy, 307 distal pancreatectomy, and 45 central or total pancreatectomy. Median sCr value was 0.86 mg/dL (range 0.30 to 14.1 mg/dL). Eighteen patients (1.7%) had severe CKD and 31 (2.9%) had sCr ≥ 1.8 mg/dL. Complications occurred in 622 patients (58.6%), major complications in 198 (18.7%), and respiratory failure in 48 (4.5%). Both severe CKD and sCr ≥ 1.8 mg/dL were associated with any complication, major complications, and respiratory failure on univariate analysis. On multivariate analysis, severe CKD was associated with increased complications (odds ratio [OR] 5.5; 95% CI 1.3 to 25.5; p = 0.02) and respiratory failure (OR 6.1; 95% CI 1.8 to 20.5; p = 0.03), but not major complications. Using sCr ≥ 1.8 mg/dL as a surrogate marker for renal insufficiency, patients with sCr ≥ 1.8 mg/dL had increased risk of any complication (OR 3.5; 95% CI 1.3 to 9.3; p = 0.01), major complications (OR 2.2; 95% CI 1.04 to 4.8; p = 0.04), and respiratory failure (OR 4.7; 95% CI 1.8 to 12.6; p = 0.002). CONCLUSIONS: Few patients with significant renal insufficiency are candidates for pancreatic resection. Severe CKD (stages 4-5) is associated with increased risk of complication and respiratory failure. Serum creatinine ≥ 1.8 mg/dL may serve as a useful marker of renal insufficiency and identifies patients at significantly increased risk of any complication, major complication, and respiratory failure after pancreatic resection.

Is it time to stop checking frozen section neck margins during pancreaticoduodenectomy?

BACKGROUND: Residual disease after pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PDAC) adversely impacts survival. The value of taking additional neck margin after a positive frozen section (FS) to achieve a negative margin remains uncertain. METHODS: All patients who underwent PD for PDAC from January 2000 August 2012 were identified and classified as negative (R0) or positive (R1) based on final neck margin. We examined factors for association with a positive FS neck margin and overall survival (OS). We assessed the value of converting an R1 neck margin to R0 via additional parenchymal resection. RESULTS: A total of 382 patients had FS neck margin analysis, of which 53 (14 %) were positive. Positive FS neck margin was associated with decreased OS (11.1 vs. 17.3 months, p = 0.01) on univariate analysis. On multivariate analysis poor histologic grade (p = 0.007), increased tumor size (p = 0.003), and a positive retroperitoneal margin (p = 0.009) were independently associated with decreased OS, but positive FS neck margin was not. Of the 53 patients with positive FS, 41 underwent additional neck resection and 23 were converted to R0. On permanent section, R0 neck margin was achieved in 322 patients (84 %), R1 in 37 patients (10 %), and R1 converted to R0 in 23 patients (6 %). Both the converted and the R1 groups had significantly poorer OS than the R0 group (11.3 vs. 11.1 vs. 17.3 months respectively; p = 0.04). CONCLUSIONS: Positive FS margin at the pancreatic neck during PD for PDAC is associated with poor survival. Extending the neck resection after a positive FS to achieve R0 margin status does not appear to improve OS.

Vein involvement during pancreaticoduodenectomy: is there a need for redefinition of "borderline resectable disease"?

INTRODUCTION: Current National Comprehensive Cancer Network guidelines recommend neoadjuvant therapy for borderline resectable pancreatic adenocarcinoma to increase the likelihood of achieving R0 resection. A consensus has not been reached on the degree of venous involvement that constitutes borderline resectability. This study compares the outcome of patients who underwent pancreaticoduodenectomy with or without vein resection without neoadjuvant therapy. METHODS: A multi-institutional database of patients who underwent pancreaticoduodenectomy was reviewed. Patients who required vein resection due to gross vein involvement by tumor were compared to those without evidence of vein involvement. RESULTS: Of 492 patients undergoing pancreaticoduodenectomy, 70 (14 %) had vein resection and 422 (86 %) did not. There was no difference in R0 resection (66 vs. 75 %, p = NS). On multivariate analysis, vein involvement was not predictive of disease-free or overall survival. CONCLUSION: This is the largest modern series examining patients with or without isolated vein involvement by pancreas cancer, none of whom received neoadjuvant therapy. Oncological outcome was not different between the two groups. These data suggest that up-front surgical resection is an appropriate option and call into question the inclusion of isolated vein involvement in the definition of "borderline resectable disease."