Quality-of-Life Evaluation After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreductive surgery (CS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastases can alleviate symptoms and prolong survival at the expense of morbidity and quality of life (QoL). This study aimed to monitor QoL and outcomes before and after HIPEC. METHODS: A prospective QoL trial of patients who underwent HIPEC for peritoneal metastases from 2000 to 2015 was conducted. The patients completed the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), the Functional Assessment of Cancer Therapy + Colon Subscale (FACT-C), the Brief Pain Inventory, the Center for Epidemiologic Studies Depression scale, and the Eastern Cooperative Oncology Group (ECOG) performance status at baseline, then 3, 6, 12, and 24 months after HIPEC. The trial outcome index (TOI) was analyzed. Proportional hazards modeled the effect of baseline QoL on survival. RESULTS: The 598 patients (53.8 % female) in the study had a mean age of 53.3 years. The overall 1-year survival rate was 76.8 %, and the median survival period was 2.9 years. The findings showed a minor morbidity rate of 29.3 %, a major morbidity rate of 21.7 %, and a 30-day mortality rate of 3.5 %. The BPI (p < 0.0001) and worst pain (p = 0.004) increased at 3 months but returned to baseline at 6 months. After CS + HIPEC, FACT-C emotional well-being, SF-36 mental component score, and emotional health improved (all p < 0.001). Higher baseline FACT-General (hazard ratio [HR], 0.92; 95 % confidence interval [CI], 0.09-0.96), FACT-C (HR, 0.73; 95 % CI 0.65-0.83), physical well-being (HR, 0.71; 95 % CI 0.64-0.78), TOI (HR, 0.87; 95 % CI 0.84-0.91), and SF-36 vitality (HR, 0.88; 95 % CI 0.83-0.92) were associated with improved survival (all p < 0.001). Higher baseline BPI (HR, 1.1; 95 % CI 1.05-1.14; p < 0.0001), worst pain (HR, 1.06; 95 % CI 1.01-1.10; p = 0.01), and ECOG (HR, 1.74; 95 % CI 1.50-2.01; p < 0.0001) were associated with worse survival. CONCLUSIONS: Although HIPEC is associated with morbidity and detriments to QoL, recovery with good overall QoL typically occurs at or before 6 months. Baseline QoL is associated with morbidity, mortality, and survival after HIPEC.

Resection and transplantation for hepatocellular carcinoma: factors influencing surgical options.

The management of hepatocellular carcinoma within the Milan criteria and with well-compensated cirrhosis is a topic of debate. Recent surveillance programs in patients with hepatitis C and cirrhosis have allowed some patients to be diagnosed with early, potentially curable, disease via liver resection (LR), liver transplantation (LT) or liver ablation. LT has excellent outcomes with 5-year survival rates >70% for patients within the Milan criteria. However, its utilization is limited by increasing organ shortages. LR is also effective with 5-year survival outcomes between 50-70% and safe in light of advances in surgical technique, preresection optimization and patient selection. Patients with solitary tumors and well-preserved liver function are good candidates for LR, whereas LT is best reserved for patients with compromised liver function and multifocal disease. LT and LR should not be viewed as competing tools but as complementary tools in the current armamentarium to treat early hepatocellular carcinoma.

A comparison of right posterior sectorectomy with formal right hepatectomy: a dual-institution study.

OBJECTIVES: Right posterior sectorectomy (RPS) preserves liver volume but typically requires a longer parenchymal transection distance than does right hepatectomy (RH). This study was conducted to define the advantages of one approach over the other. METHODS: Databases at two institutions were retrospectively reviewed for all patients submitted to RPS or RH between January 2000 and August 2012. Primary outcomes were perioperative complications and 90-day mortality. RESULTS: Patients undergoing RPS (n = 100) and RH (n = 480), respectively, were similar in demographics, comorbidities, operative indications and Model for End-stage Liver Disease (MELD) mean scores (7.8 in the RPS group and 7.7 in the RH group; P = 0.49). A comparison of the RPS group with the RH group showed no significant differences in mean estimated blood loss (697 ml versus 713 ml; P = 0.900), rate of transfusions (19.2% versus 17.1%; P = 0.720), margin-positive resection (9.2% versus 11.6%; P = 0.70), complications (41.8% versus 42.0%; P = 1.000), bile leak (3.0% versus 4.0%; P = 1.000), or length of stay (7.5 days versus 8.3 days; P = 0.360). Postoperative hepatic insufficiency (defined as a postoperative bilirubin level of >7 mg/dl or significant ascites), occurred less frequently after RPS (1.0% versus 8.5%; P = 0.005). Operation type remained an independent determinant of postoperative hepatic insufficiency after controlling for preoperative risk factors (RH: hazard ratio = 9.628, 95% confidence interval 1.295-71.573; P = 0.027). A total of 28 (4.8%) patients died within 90 days; these included 25 (5.2%) patients in the RH group and three (3.0%) in the RPS group (P = 0.449). CONCLUSIONS: Despite similar blood loss and overall morbidity, RPS is associated with less hepatic insufficiency than RH. Right posterior sectorectomy is parenchyma-sparing and should be strongly considered when it is technically feasible and oncologically sound.

VIP down-regulates the inflammatory potential and promotes survival of dying (neural crest-derived) corneal endothelial cells ex vivo: necrosis to apoptosis switch and up-regulation of Bcl-2 and N-cadherin.

The neuropeptide vasoactive intestinal peptide (VIP) is anti-inflammatory and protective in the immune and nervous systems, respectively. This study demonstrated in corneal endothelial (CE) cells injured by severe oxidative stress (1.4 mM H(2)O(2)) in bovine corneal organ cultures that VIP pre-treatment (0, 10(-10), 10(-8), and 10(-6) M; 15 min), in a VIP concentration-dependent manner, switched the inflammation-causing necrosis to inflammation-neutral apoptosis (showing annexin V-binding, chromatin condensation, and DNA fragmentation) and upheld ATP levels in a VIP antagonist (SN)VIPhyb-sensitive manner, while up-regulated mRNA levels of the anti-apoptotic Bcl-2 and the differentiation marker N-cadherin in a kinase A inhibitor-sensitive manner. As a result, VIP, in a concentration-dependent and VIP antagonist-sensitive manners, promoted long-term CE cell survival. ATP levels, a determining factor in the choice of apoptosis versus necrosis, measured after VIP pre-treatment and 0.5 min post-H(2)O(2) were 39.6 +/- 3.3, 50.8 +/- 6.2, 60.1 +/- 4.8, and 53.6 +/- 5.3 pmoles/microg protein (mean +/- SEM), respectively (p < 0.05, anova). VIP treatment alone concentration-dependently increased levels of N-cadherin (Koh et al. 2008), the phosphorylated cAMP-responsive-element binding protein and Bcl-2, while 10(-8) M VIP, in a VIP antagonist (SN)VIPhyb-sensitive manner, increased ATP level by 38% (p < 0.02) and decreased glycogen level by 32% (p < 0.02). VPAC1 (not VPAC2) receptor was expressed in CE cells. Thus, CE cell VIP/VPAC1 signaling is both anti-inflammatory and protective in the corneal endothelium.

Effect of Negative Pressure Wound Therapy on Wound Complications Post-Pancreatectomy.

Surgical site infection (SSI) and incisional hernia are common complications after major pancreatectomy. We investigated the effects of negative pressure wound therapy (NPWT) on short- and long-term wound outcomes in patients undergoing pancreatectomy. A randomized controlled trial comparing the effect of NPWT with standard surgical dressing (SSD) on wounds was performed in 265 patients undergoing open gastrointestinal resections from 2012 to 2016. We performed a subset analysis of 73 patients who underwent pancreatectomy. Wound complications in the first 30 days and incisional hernia rates were assessed. There were 33 (45%) female patients in the study and the average BMI was 27.6. The pancreaticoduodectomy rate was 68 per cent, whereas 27 per cent of patients underwent distal or subtotal pancreatectomy, and 4 per cent total pancreatectomy. Incisional hernia rates were 32 per cent and 14 per cent between the SSD and NPWT groups, respectively (P = 0.067). In the SSD (n = 37) and NPWT (n = 36) cohorts, the superficial SSI, deep SSI, seroma, and dehiscence rates were 16 per cent and 14 per cent (P > 0.99), 5 per cent and 8 per cent (P = 0.67), 16 per cent and 11 per cent (P = 0.74), and 5 per cent and 3 per cent (P ≥ 0.99), respectively. After adjusting for pancreatic fistula and delayed gastric emptying, no statistically significant differences in the primary outcomes were observed. These findings were true irrespective of the type of resection performed. Short- and long-term wound complications were not improved with NPWT. We observed a trend toward decreased incisional hernia rates in patients treated with NPWT. Owing to the multifactorial nature of wound complications, it is yet to be determined which cohorts of pancreatectomy patients will benefit from NPWT.

Phase II Randomized Trial of Negative-Pressure Wound Therapy to Decrease Surgical Site Infection in Patients Undergoing Laparotomy for Gastrointestinal, Pancreatic, and Peritoneal Surface Malignancies.

BACKGROUND: Surgical site infections (SSIs) remain a major source of morbidity and cost after resection of intra-abdominal malignancies. Negative-pressure wound therapy (NPWT) has been reported to significantly reduce SSIs when applied to the closed laparotomy incision. This article reports the results of a randomized clinical trial examining the effect of NPWT on SSI rates in surgical oncology patients with increased risk for infectious complications. STUDY DESIGN: From 2012 to 2016, two hundred and sixty-five patients who underwent open resection of intra-abdominal neoplasms were stratified into 3 groups: gastrointestinal (n = 57), pancreas (n = 73), or peritoneal surface (n = 135) malignancy. They were randomized to receive NPWT or standard surgical dressing (SSD) applied to the incision from postoperative days 1 through 4. Primary outcomes of combined incisional (superficial and deep) SSI rates were assessed up to 30 days after surgery. RESULTS: There were no significant differences in superficial SSIs (12.8% vs 12.9%; p > 0.99) or deep SSI (3.0% vs 3.0%; p > 0.99) rates between the SSD and NPWT groups, respectively. When stratified by type of surgery, there were still no differences in combined incisional SSI rates for gastrointestinal (25% vs 24%; p > 0.99), pancreas (22% vs 22%; p > 0.99), and peritoneal surface malignancy (9% vs 9%; p > 0.99) patients. When performing univariate and multivariate logistic regression analysis of demographic and operative factors for the development of combined incisional SSI, the only independent predictors were preoperative albumin (p = 0.0031) and type of operation (p = 0.018). CONCLUSIONS: Use of NPWT did not significantly reduce incisional SSI rates in patients having open resection of gastrointestinal, pancreatic, or peritoneal surface malignancies. Based on these results, at this time NPWT cannot be recommended as a therapeutic intervention to decrease infectious complications in these patient populations.

Impact of adjuvant external beam radiotherapy on survival in surgically resected gallbladder adenocarcinoma: a propensity score-matched Surveillance, Epidemiology, and End Results analysis.

BACKGROUND: We sought to define the utilization and effect of adjuvant external-beam radiotherapy (XRT) on patients having undergone curative-intent resection for gallbladder cancer (GBC). METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 5,011 patients with GBC who underwent resection between 1988 and 2009. The impact of XRT on survival was analyzed by the use of propensity-score matching by comparing clinicopathologic factors between patients who received resection only versus resection plus XRT. RESULTS: Median age was 72 years, and most patients were female (73.4%); 66.2% patients had intermediate to poorly differentiated tumors, and 19.1% had lymph node metastasis. The majority (75.0%) had "localized" disease by Surveillance, Epidemiology, and End Results classification. A total of 899 patients (17.9%) received XRT whereas 4,112 patients did not. Factors associated with receipt of XRT were younger age (odds ratio [OR] 5.33), tumor extension beyond the serosa (OR 1.55), intermediate- to poorly differentiated tumors (OR 1.56), and lymph node metastasis (OR 2.59) (all P < .05). Median and 1-year survival were 15 months and 59.0%, respectively. On propensity-matched multivariate model, despite having more advanced tumors, XRT was independently associated with better long-term survival at 1 year (hazard ratio 0.45; P < .001), but not 5 years (hazard ratio 1.06; P = .50). CONCLUSION: A total of 18% of patients with GBC received XRT after curative intent surgery. The use of adjuvant XRT was associated with a short-term survival benefit, but the benefit dissipated over time.

Referral patterns and treatment choices for patients with hepatocellular carcinoma: a United States population-based study.

BACKGROUND: Patterns of care of physician specialists may differ for patients with hepatocellular carcinoma (HCC). Reasons underlying variations are poorly understood. One source of variation may be disparate referral rates to specialists, leading to differences in cancer-directed treatments. STUDY DESIGN: Surveillance, Epidemiology, and End Results (SEER)-linked Medicare database was queried for patients with HCC, diagnosed between 1998 and 2007, who consulted 1 or more physicians after diagnosis. Visit and procedure records were abstracted from Medicare billing records. Factors associated with specialist consult and subsequent treatment were examined. RESULTS: There were 6,752 patients with HCC identified; 1,379 (20%) patients had early-stage disease. Median age was 73 years; the majority were male (66%), white (60%), and from the West region (56%). After diagnosis, referral to a specialist varied considerably (hepatology/gastroenterology, 60%; medical oncology, 62%; surgery, 56%; interventional radiology [IR], 33%; radiation oncology, 9%). Twenty-two percent of patients saw 1 specialist; 39% saw 3 or more specialists. Time between diagnosis and visitation with a specialist varied (surgery, 37 days vs IR, 55 days; p = 0.04). Factors associated with referral to a specialist included younger age (odds ratio [OR] 2.16), Asian race (OR 1.49), geographic region (Northeast OR 2.10), and presence of early-stage disease (OR 2.21) (all p < 0.05). Among patients with early-stage disease, 77% saw a surgeon, while 50% had a consultation with medical oncologist. Receipt of therapy among patients with early-stage disease varied (no therapy, 30%; surgery, 39%; IR, 9%; chemotherapy, 23%). Factors associated with receipt of therapy included younger age (OR 2.48) and early-stage disease (OR 2.20). CONCLUSIONS: After HCC diagnosis, referral to a specialist varied considerably. Both clinical and nonclinical factors were associated with consultation. Disparities in referral to a specialist and subsequent therapy need to be better understood to ensure all HCC patients receive appropriate care.

Trends and patterns of utilization in post-treatment surveillance imaging among patients treated for hepatocellular carcinoma.

BACKGROUND: Little is known about the patterns of utilization of surveillance imaging after treatment of hepatocellular carcinoma (HCC). We sought to define population-based patterns of surveillance and investigate if intensity of surveillance impacted outcome following HCC treatment. METHODS: The Surveillance, Epidemiology, and End Results-Medicare database was used to identify patients with HCC diagnosed between 1998 and 2007 who underwent resection, ablation, or intra-arterial therapy (IAT). The association between imaging frequency and long-term survival was analyzed. RESULTS: Of the 1,467 patients, most underwent ablation only (41.5%), while fewer underwent liver resection only (29.6 %) or IAT only (18.3%). Most patients had at least one CT scan (92.7%) during follow-up, while fewer had an MRI (34.1%). A temporal trend was noted with more frequent surveillance imaging obtained in post-treatment year 1 (2.5 scans/year) vs. year 5 (0.9 scans/year; P = 0.01); 34.5% of alive patients had no imaging after 2 years. Frequency of surveillance imaging correlated with procedure type (total number of scans/5 years, resection, 4.7; ablation, 4.9; IAT, 3.7; P < 0.001). Frequency of surveillance imaging was not associated with a survival benefit (three to four scans/year, 49.5 months vs. two scans/year, 71.7 months vs. one scan/year, 67.6 months; P = 0.01) CONCLUSION: Marked heterogeneity exists in how often surveillance imaging is obtained following treatment of HCC. Higher intensity imaging does not confer a survival benefit.

Provider versus patient factors impacting hospital length of stay after pancreaticoduodenectomy.

BACKGROUND: Studies reporting perioperative outcomes after pancreaticoduodenectomy (PD) have focused on morbidity and mortality. Understanding factors that impact hospital duration of stay may have cost-saving implications. We sought to examine variation in duration of stay after PD occurring at the patient, surgeon, and hospital levels. METHODS: Year-specific PD volumes for both surgeons and hospitals were determined from the 2003-2009 Nationwide Inpatient Sample and grouped into terciles. Patient age, gender, and comorbidities were examined. Median duration of stay was calculated and modified Poisson regression examined factors associated with duration of stay. RESULTS: Among 5,190 individuals undergoing PD, median age was 65 years and 49.3% were female. Median duration of stay was 13 days (range, 0-234). Older patients and those with comorbid illness were more likely to have duration of stay of ≥ 14 days (P < .001). Median annual surgeon volume was 8 (interquartile range [IQR], 2-19; range, 1-54). Annual hospital volume ranged from 1 to 129 (median, 18; IQR, 6-52). Both low surgeon and hospital PD volume were associated with longer durations of stay (P < .001). In multivariable modeling, age remained associated with duration of stay (relative risk [RR], 1.007 per year; P < .001); however, comorbidity did not. Patients operated on by high-volume surgeons (RR, 0.67) or at high-volume hospitals (RR, 0.75) had a reduced risk of a prolonged duration of stay of ≥ 14 days (both P < .001). CONCLUSION: PD patients treated by higher volume surgeons and at higher volume hospitals had a shorter duration of stay. Although some patient-level factors impact duration of stay after PD, nonclinical factors such as surgeon and hospital volume were also important contributors to duration of stay.

Post-treatment surveillance of patients with colorectal cancer with surgically treated liver metastases.

BACKGROUND: Little is known about current surveillance patterns after treatment of colorectal liver metastasis (CRLM) or whether the intensity of surveillance correlates with outcome. We sought to define current population-based patterns of surveillance and investigate whether intensity of surveillance impacted outcome. METHODS: We queried the Surveillance, Epidemiology, and End Results-linked Medicare database for patients with CRLM diagnosed between 1991 and 2005 who underwent liver resection and/or tumor ablation. Frequency of post-treatment abdominal computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) was recorded for ≤ 5 years after treatment. The association between frequency of imaging with secondary interventions and long-term survival were analyzed. RESULTS: We identified 1,739 patients with CRLM treated with surgery; median age was 73 years, and the majority were male (52.6%). CRLM treatment consisted of liver resection (61%), ablation (32%), or both simultaneously (6%). CT (97%) was utilized more often for post-treatment surveillance compared with MRI (7%) and PET (18%). A temporal trend was noted with more frequent surveillance imaging obtained in post-treatment year 1 (2.4 scans/year) versus year 5 (0.6 scans/year; P = .01); 66% of living patients had no imaging after 2 years. Frequency of surveillance imaging correlated with procedure type (total number of scans/5 years: resection, 5.0; ablation, 4.6; resection and ablation, 6.2; P = .01). Other factors associated with a greater frequency of surveillance included younger age at diagnosis, geographic location in the South, and CRLM directed surgery in 2000 through 2005 (all P < .05). Overall survival did not differ by intensity of surveillance imaging (3-4 scans/yr, 43 months vs 2 scans/yr, 57 months vs 1 scan/yr, 54 months; P = .08). CONCLUSION: Marked heterogeneity exists in how often surveillance imaging is obtained after treatment of CRLM. Intensity of imaging does not affect time to second procedure or median survival duration. Surveillance guidelines for CRLM need to be refocused to provide the best value for healthcare resources.

Impact of sarcopenia on outcomes following intra-arterial therapy of hepatic malignancies.

BACKGROUND: Assessment of patient performance status is often subjective. Sarcopenia--measurement of muscle wasting--may be a more objective means to assess performance status and therefore mortality risk following intra-arterial therapy (IAT). METHODS: Total psoas area (TPA) was measured on cross-sectional imaging in 216 patients undergoing IAT of hepatic malignancies between 2002 and 2012. Sarcopenia was defined as TPA in the lowest sex-specific quartile. Impact of sarcopenia was assessed relative to other clinicopathological factors. RESULTS: Indications for IAT included hepatocellular carcinoma (51 %), intrahepatic cholangiocarcinoma (13 %), colorectal liver metastasis (7 %), or other metastatic disease (30 %). Median TPA among men (568 mm(2)/m(2)) was greater than women (413 mm(2)/m(2)). IAT involved conventional chemoembolization (54 %), drug-eluting beads (40 %), or yttrium-90 (6 %). Median tumor size was 5.8 cm; most patients had multiple lesions (74 %). Ninety-day mortality was 9.3 %; 3-year survival was 39 %. Factors associated with risk of death were tumor size (HR = 1.84) and Child's score (HR = 2.15) (all P < 0.05). On multivariate analysis, sarcopenia remained independently associated with increased risk of death (lowest vs. highest TPA quartile, HR = 1.84; P = 0.04). Sarcopenic patients had a 3-year survival of 28 vs. 44 % for non-sarcopenic patients. CONCLUSIONS: Sarcopenia was an independent predictor of mortality following IAT with sarcopenic patients having a twofold increased risk of death. Sarcopenia is an objective measure of frailty that can help clinical decision-making regarding IAT for hepatic malignancies.

Influence of patient, physician, and hospital factors on 30-day readmission following pancreatoduodenectomy in the United States.

UNLABELLED: IMPORTANCE It is not known whether hospital and surgeon volumes have an association with readmission among patients undergoing pancreatoduodenectomy. OBJECTIVE: To evaluate patient-, surgeon-, and hospital-level factors associated with readmission. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare data with cases diagnosed from January 1, 1998, to December 31, 2005, and followed up until December 2007. Population-based cancer registry data were linked to Medicare data for the corresponding patients. A total of 1488 unique individuals who underwent a pancreatoduodenectomy were identified. INTERVENTIONS: Undergoing pancreatoduodenectomy at hospitals classified by volume of pancreatoduodenectomy procedures performed at the facility were either very-low, low, medium, or high volume. Undergoing pancreatoduodenectomy by surgeons classified by volume of pancreatoduodenectomy procedures performed by the surgeon were either very-low, low, medium, or high volume. MAIN OUTCOMES AND MEASURES: In-hospital morbidity, mortality, and 30-day readmission were examined. RESULTS: The median age was 74 years, and 1436 patients (96.5%) had a least 1 medical comorbidity. Patients were treated by 575 distinct surgeons at 298 distinct hospitals. Length of stay was longest (median, 17 days) and 90-day mortality highest (17.2%) at very-low-volume hospitals (P < .001). Among all pancreatoduodenectomy patients, 292 (21.3%) were readmitted within 30 days of discharge. There was no effect of surgeon volume and a modest effect of hospital volume (odds ratio for highest- vs lowest-volume quartiles, 1.85; 95% CI, 1.22-2.80; P = .02). The presence of significant preoperative medical comorbidities was associated with an increased risk for hospital readmission after pancreatoduodenectomy. A comorbidity score greater than 13 had a pronounced effect on the chance of readmission following pancreatoduodenectomy (odds ratio, 2.06; 95% CI, 1.56-2.71; P < .001). The source of variation in readmission was primarily attributable to patient-related factors (95.4%), while hospital factors accounted for 4.3% of the variability and physician factors for only 0.3%. CONCLUSIONS AND RELEVANCE: Nearly 1 in 5 patients are readmitted following pancreatoduodenectomy. While variation in readmission is, in part, attributable to differences among hospitals, the largest share of variation was found at the patient level.