Pancreatic Metastasis from Adenocarcinoma of the Uterine Cervix.

Pancreatic metastasis from cervical cancer is extremely rare. We report a case of metastatic adenocarcinoma of the pancreas from uterine cervical cancer. A 70-year-old woman was referred because of a pancreatic mass detected by CT. She had been diagnosed with uterine cervical adenocarcinoma 20 months previously. After concurrent chemoradiotherapy, CT showed no evidence of the cervical mass, and follow-up showed no evidence of recurrence. Endoscopic ultrasound-guided fine needle aspiration biopsy of the pancreatic mass resulted in a diagnosis of metastatic adenocarcinoma from uterine cervix.

Plasma CRABP2 as a Novel Biomarker in Patients with Non-Small Cell Lung Cancer.

BACKGROUND: Lung cancer is the most common cause of cancer-related mortality worldwide. We previously reported the identification of a new genetic marker, cellular retinoic acid binding protein 2 (CRABP2), in lung cancer tissues. The aim of this study was to assess plasma levels of CRABP2 from patients with non-small cell lung cancer (NSCLC). METHODS: Blood samples that were collected from 122 patients with NSCLC between September 2009 and September 2013 were selected for the analysis, along with samples from age- (± 5 years), sex-, and cigarette smoking history (± 10 pack-years [PY])-matched controls from the Korea Biobank Network. The control specimens were from patients who were without malignancies or pulmonary diseases. We measured plasma levels of CRABP2 using commercially available enzyme-linked immunosorbent assay kits. RESULTS: The mean age of the NSCLC patients was 71.8 ± 8.9 years, and the median cigarette smoking history was 32 PY (range, 0-150 PY). Plasma CRABP2 levels were significantly higher in patients with NSCLC than in the matched controls (37.63 ± 28.71 ng/mL vs. 24.09 ± 21.09 ng/mL, P < 0.001). Higher plasma CRABP2 levels were also correlated with lower survival rates in NSCLC patients (P = 0.014). CONCLUSION: Plasma CRABP2 levels might be a novel diagnostic and prognostic marker in NSCLC.

Impact of a trimodal prehabilitation program on functional recovery after colorectal cancer surgery: a pilot study.

BACKGROUND: Patients undergoing colorectal cancer resections are at risk for delayed recovery. Prehabilitation aims to enhance functional capacity preoperatively for better toleration of surgery and to facilitate recovery. The authors previously demonstrated the limited impact of a prehabilitation program using exercise alone. They propose an expanded trimodal prehabilitation program that adds nutritional counseling, protein supplementation, and anxiety reduction to a moderate exercise program. This study aimed to estimate the impact of this trimodal program on the recovery of functional capacity compared with standard surgical care. METHODS: Consecutive patients were enrolled in this pre- and postintervention study over a 23-month period. The postoperative recovery for 42 consecutive patients enrolled in the prehabilitation program was compared with that of 45 patients assessed before the intervention began. The primary outcome was functional walking capacity (6-min walk test [6MWT]). The secondary outcomes included self-reported physical activity (CHAMPS questionnaire) and health-related quality of life (SF-36). Data are expressed as mean ± standard deviation or median (interquartile range [IQR]) and were analyzed using Chi-square and Student's t test. All p values lower than 0.05 were considered significant. RESULTS: The prehabilitation and control groups were comparable in terms of age, gender, body mass index (BMI) and American Society of Anesthesiology (ASA) class. There was no difference in walking capacity at the first assessment (6MWT distance, 422 ± 87 vs 402 ± 57 m; p = 0.21). During the prehabilitation period lasting a median of 33 days (range, 21-46 days), functional walking capacity improved by 40 ± 40 m (p < 0.01). The postoperative complication rates and the hospital length of stay were similar. The patients in the prehabilitation program had better postoperative walking capacity at both 4 weeks (mean difference, 51.5 ± 93 m; p = 0.01) and 8 weeks (mean difference, 84.5 ± 83 m; p < 0.01). At 8 weeks, 81 % of the prehabilitated patients were recovered compared with 40 % of the control group (p < 0.01). The prehabilitation group also reported higher levels of physical activity before and after surgery. CONCLUSION: In this pilot study, a 1-month trimodal prehabilitation program improved postoperative functional recovery. A randomized trial is ongoing (NCT01356264).

Understanding the Determinants of Weight-Related Quality of Life among Bariatric Surgery Candidates.

Obesity and its relation to quality of life are multifaceted. The purpose of this paper was to contribute evidence to support a framework for understanding the impact of obesity on quality of life in 42 morbidly obese subjects considering a wide number of potential determinants. A model of weight-related quality of life (WRQL) was developed based on the Wilson-Cleary model, considering subjects' weight characteristics, arterial oxygen pressure (PaO(2)), walking capacity (6-minute walk test, 6MWT), health-related quality of life (HRQL; Physical and Mental Component Summaries of the SF-36 PCS/MCS), and WRQL. The model of WRQL was tested with linear regressions and a path analysis, which showed that as PaO(2) at rest increased 6MWT increased. 6MWT was positively associated with the PCS, which in turn was positively related to WRQL along with the MCS. The model showed good fit and explained 38% of the variance in WRQL.

Impact of preoperative change in physical function on postoperative recovery: argument supporting prehabilitation for colorectal surgery.

BACKGROUND: Abdominal surgery represents a physiologic stress and is associated with a period of recovery during which functional capacity is often diminished. "Prehabilitation" is a program to increase functional capacity in anticipation of an upcoming stressor. We reported recently the results of a randomized trial comparing 2 prehabilitation programs before colorectal surgery (stationary cycling plus weight training versus a recommendation to increase walking coupled with breathing exercises); however, adherence to the programs was low. The objectives of this study were to estimate: (1) the extent to which physical function could be improved with either prehabilitation program and identify variables associated with response; and (2) the impact of change in preoperative function on postoperative recovery. METHODS: This study involved a reanalysis of data arising from a randomized trial. The primary outcome measure was functional walking capacity measured by the Six-Minute Walk Test; secondary outcomes were anxiety, depression, health-related quality of life, and complications (Clavien classification). Multiple linear regression was used to estimate the extent to which key variables predicted change in functional walking capacity over the prehabilitation and follow-up periods. RESULTS: We included 95 people who completed the prehabilitation phase (median, 38 days; interquartile range, 22-60), and 75 who were also evaluated postoperatively (mean, 9 weeks). During prehabilitation, 33% improved their physical function, 38% stayed within 20 m of their baseline score, and 29% deteriorated. Among those who improved, mental health, vitality, self-perceived health, and peak exercise capacity also increased significantly. Women were less likely to improve; low baseline walking capacity, anxiety, and the belief that fitness aids recovery were associated with improvements during prehabilitation. In the postoperative phase, the patients who had improved during prehabilitation were also more likely to have recovered to their baseline walking capacity than those with no change or deterioration (77% vs 59% and 32%; P = .0007). Patients who deteriorated were at greater risk of complications requiring reoperation and/or intensive care management. Significant predictors of poorer recovery included deterioration during prehabilitation, age >75 years, high anxiety, complications requiring intervention, and timing of follow-up assessment. CONCLUSION: In a group of patients undergoing scheduled colorectal surgery, meaningful changes in functional capacity can be achieved over several weeks of prehabilitation. Patients and those who care for them, especially those with poor physical capacity, should consider a prehabilitation regimen to enhance functional exercise capacity before colectomy.

Prior intense exercise reduces arterial carbon dioxide pressure in extreme obesity.

PURPOSE: Unlike normal weight individuals, individuals with extreme obesity do not show a decrease in arterial carbon dioxide pressure (PaCO2) from rest to peak exercise. This indicates that breathing is compromised. The objective of this study was to determine if prior high intensity exercise lowers PaCO2 in comparison with a first bout, normalized for the same metabolic rate. METHODS: Oxygen consumption during incremental, ramped exercise was matched to constant workload exercise (75% of peak power). Both protocols were to volitional exhaustion 39 ± 8 min apart. Eleven obese subjects (BMI = 47 ± 8 kg/m², aerobic capacity = 2.3 ± 0.6 L/min) were evaluated. Forty paired samples were obtained at the same metabolic rate between the two protocols. RESULTS: The mean absolute difference and 95% CI were large for arterial oxygen pressure (PaO2) = 9 (6, 11) mmHg and alveolar to arterial oxygen pressure difference (AaDO2) = 7 (5, 8) mmHg. The mean absolute difference for arterial oxyhemoglobin saturation (%SaO2) = 0.5 (0.4, 0.7) %; PaCO2 = 4 (3, 4) mmHg; physiological dead space to tidal volume ratio (VD/VT) = 0.04 (0.03, 0.05); and alveolar ventilation (VA) = 3 (2, 4) L/min. The recovery period after the first bout of exercise reduced the PaCO2 by 3 mmHg when matched for similar metabolic rates. Constant workload exercise predicted VA, %SaO2, V(D)/V(T), and PaCO2, but not PaO2 or AaDO2 during incremental exercise at similar metabolic rates. CONCLUSION: Given a sufficient chemical stimulus, obese subjects will attempt to breathe more, although this does not mean more VA, which removes CO2.

Responsive measures to prehabilitation in patients undergoing bowel resection surgery.

Surgical patients often show physiological and metabolic distress, muscle weakness, and long hospital stays. Physical conditioning might help recovery. We attempted to identify the most responsive measure of aerobic fitness from a four-week pre-surgical aerobic exercise program (prehabilitation) in patients undergoing major bowel resection. Twenty-one subjects randomized two to one (exercise: control) scheduled for colorectal surgery. Fourteen subjects [Body Mass Index (BMI) = 27 +/- 6 kg/m(2); maximal oxygen uptake (VO(2max)) = 22 +/- 10 ml/kg/min] underwent 3.8 +/- 1.2 weeks (27 +/- 8 sessions) of progressive, structured pre-surgical aerobic exercise training at 40 to 65% of heart rate reserve (%HRR). Peak power output was the only maximal measure that was responsive to training [26 +/- 27%, Effects Size (ES) = 0.24; Standardized Response Mean (SRM) = 1.05; p < 0.05]. For the submaximal measures, heart rate and oxygen uptake during submaximal exercise was most responsive to training (decrease by 13% +/- 15%, ES = -0.24; SRM = -0.57; and 7% +/- 6%, ES = -0.40; SRM -0.97; p < 0.05) at an exercise intensity of 76 +/- 47 W. There was no change to maximal or submaximal measures in the control group. The distance walked over six minutes improved in both groups (by approximately 30 m), but the effect size and t-statistic were higher in the exercise group. Heart rate and oxygen uptake during submaximal exercise, and peak power output are the most responsive measures to four weeks of prehabilitation in subjects with low initial fitness.

Preoperative gender differences in pulmonary gas exchange in morbidly obese subjects.

BACKGROUND: Morbidly obese men may have poorer pulmonary gas exchange compared to morbidly obese women (see Zavorsky et al., Chest 131:362-367, 2007). The purpose was to compare pulmonary gas exchange in morbidly obese men and women at rest and throughout exercise. METHODS: Twenty-five women (age=38+/-10 years, 164+/-7 cm, body mass index or BMI = 51+/-7 kg/m(2), peak oxygen consumption or VO(2peak)=2.0+/-0.4 l/min) and 17 men (age=43+/-9 years, 178+/-7 cm, BMI=50+/-10 kg/m(2), VO(2peak)=2.6+/-0.8 l/min) were recruited to perform a graded exercise test on a cycle ergometer with temperature-corrected arterial blood-gas samples taken at rest and every minute of exercise, including peak exercise. RESULTS: At rest, women were 98% predicted for pulmonary diffusion compared to 88% predicted in men. At rest, women had better pulmonary gas exchange compared to the men which was related to women having a lower waist-to-hip ratio (WHR; p<0.01). Only 20% of the subjects had an excessive alveolar-to-arterial oxygen partial pressure difference (>or=25 mmHg) at peak exercise, but 75% of the subjects showed inadequate compensatory hyperventilation at peak exercise (arterial carbon dioxide pressure >35 mmHg), and both were not different between genders. CONCLUSION: At rest, morbidly obese men have poorer pulmonary gas exchange and pulmonary diffusion compared to morbidly obese women. The better gas exchange in women is related to the lower WHR in the women. During exercise, few subjects showed disturbances in pulmonary gas exchange despite demonstrating poor compensatory hyperventilation at peak exercise.

Compensatory exercise hyperventilation is restored in the morbidly obese after bariatric surgery.

BACKGROUND: Morbidly obese individuals may have poor compensatory hyperventilation during exercise. The objective was to examine pulmonary gas exchange and the compensatory hyperventilatory response during exercise pre- and post-weight reduction surgery in obese subjects. METHODS: Fifteen patients (age=39+/-8 years, body mass index=47+/-6 kg/m2), with an excess weight of 69+/-17 kg, were recruited. Pulmonary function at rest was assessed and arterial-blood gases were sampled at rest and all levels of exercise pre- and 10+/-3 weeks postsurgery. RESULTS: There was a loss of excess weight 21+/-6 kg (p<0.01). Waist and hip circumference decreased by 13+/-9 and 8+/-7 cm, respectively (p<0.01). Prior to surgery, there was no compensatory hyperventilation between rest and peak exercise as arterial PCO2 (PaCO2) remained unchanged (37+/-3 mm Hg). However, postsurgery, there was compensatory hyperventilation as PaCO2 decreased to 33+/-2 mm Hg at peak exercise (p<0.01), with no change in peak oxygen consumption (VO2peak in L/min). Multiple linear regression revealed that the restored ventilatory response to exercise was most strongly associated with the reduction in overall fat mass (adjusted r2=0.25; p=0.03). Total weight loss of 21 kg induces adequate compensatory hyperventilation that begins to show at about 50% of VO2peak, resulting in improved gas exchange at moderate to peak exercise intensities. CONCLUSION: Improvement in compensatory hyperventilation is most closely related to loss in overall fat mass.

Alveolar-membrane diffusing capacity improves in the morbidly obese after bariatric surgery.

BACKGROUND: Morbidly obese individuals may have impaired alveolar-membrane diffusing capacity (DmCO). The purpose of this study was to measure pulmonary diffusing capacity for NO (DLNO) as an index of DmCO pre- and postbariatric surgery in the morbidly obese. METHODS: Twenty-one patients [age = 40 +/- 9 years, body mass index (BMI) = 48.5 +/- 7.2 kg/m2] with an excess weight of 72 +/- 17 kg scheduled for bariatric surgery were recruited. Pulmonary function and arterial blood-gases were measured pre- and postsurgery. RESULTS: DmCO was 88 +/- 23% of predicted before surgery (p < 0.05). There was loss in BMI and excess weight of 7.7 +/- 2.0 kg/m2 and 31 +/- 8%, respectively. Because DmCO = DLNO/2.42, the increase in DLNO postsurgery resulted in a normalization of the predicted DmCO to 97 +/- 29% predicted, or an improvement of DLNO by 11 +/- 18 (95% CI = 3.5, 19.1; p = 0.01) milliliters per minute per millimeter of mercury without any improvement in DLCO. The DLNO/DLCO ratio and alveolar volume both increased, respectively (p < 0.05), and pulmonary capillary blood volume to DmCO ratio decreased postsurgery (p < 0.01). Multiple linear regression revealed that the change in DLNO was most strongly associated with changes in alveolar volume and the waist-to-hip ratio (adjusted r2 = 0.76; p < 0.001) and was not related to the reduction in the alveolar-to-arterial PO2 difference. CONCLUSION: Alveolar-membrane diffusion normalizes within 10 weeks after bariatric surgery. This is likely due to the increase in alveolar volume from the reduction in the waist-to-hip ratio.

Intraoperative infusion of lidocaine reduces postoperative fentanyl requirements in patients undergoing laparoscopic cholecystectomy.

BACKGROUND: Lidocaine has been shown to inhibit neural conduction and to have anti-inflammatory properties. The purpose of this study was to determine whether intraoperative lidocaine infusion reduces opioid consumption in the postanesthesia care unit (PACU). METHODS: Fifty patients were enrolled in this prospective, randomized and observer-blinded study. At induction of anesthesia the control group (n = 25) received fentanyl 3 microg.kg(-1) while the lidocaine group received fentanyl 1.5 microg.kg(-1) and a bolus of lidocaine 1.5 mg.kg(-1) followed by a continuous infusion of lidocaine 2 mg.kg(-1).hr(-1). General anesthesia included propofol, rocuronium, and desflurane titrated to maintain blood pressure and heart rate within set parameters, and the bispectral index between 35 and 50. No supplemental opioids were given during surgery. All patients received acetaminophen, ketorolac, dexamethasone, droperidol and local anesthetics in the skin incision. Patients received fentanyl and ondansetron in the PACU. The primary outcome variable was the amount of fentanyl required in the PACU to establish and to maintain visual analogue scale pain scores < 3. RESULTS: Most patients received fentanyl for pain relief in the PACU, but the cumulative mean dose was lower in the lidocaine group compared to the control group (98 +/- 54 microg, vs 154 +/- 99 microg, respectively, P = 0.018). Lidocaine infusion reduced by 10% the amount of desflurane required (P = 0.012). White-Song scores > 12 were attained by all patients in both groups within 30 min of their arrival in the PACU. Median time from arrival to the PACU to discharge home was similar in both groups, 167.5 min in the control group vs 180 min in the lidocaine group (P = 0.649). CONCLUSION: Intraoperative lidocaine infusion reduces opioid consumption in the PACU and intraoperative requirements of desflurane.

Poor compensatory hyperventilation in morbidly obese women at peak exercise.

This study was designed to compare differences in pulmonary gas exchange at rest and at peak exercise in two groups of women: (1) physically active, non-obese women and (2) women with morbid obesity. Fourteen morbidly obese women (body mass index or BMI=49+/-7 kg/m2; peak oxygen consumption or VO2 peak=14+/-2 ml/(kg min)) and 14 physically active non-obese women (BMI=22+/-2 kg/m2; VO2 peak=50+/-6 ml/(kg min)) performed an incremental, ramped exercise test to exhaustion on a cycle ergometer. Arterial blood was sampled at rest and at peak exercise. At rest, the alveolar to arterial oxygen partial pressure difference was 3x higher in the obese women (14+/-10 mmHg) compared to non-obese women (5+/-4 mmHg). Arterial carbon dioxide pressure (PaCO2) was identical in both groups at rest (37+/-4 mmHg). Only the non-obese women showed a decrease in PaCO2 rest to peak exercise (-5+/-3 mmHg). The slope between heart rate and VO2 during exercise was higher in the morbidly obese compared to non-obese women indicating that for the same absolute increase in VO2 a larger increase in heart rate is needed, demonstrating poorer cardiac efficiency in obese women. In conclusion, morbidly obese women have poorer exercise capacity, cardiac efficiency, and compensatory hyperventilation at peak exercise, and poorer gas exchange at rest compared to physically active, non-obese women.

Waist-to-hip ratio is associated with pulmonary gas exchange in the morbidly obese.

BACKGROUND: Morbidly obese individuals (ie, body mass index [BMI], > or = 40 kg/m2) may have a pulmonary gas exchange impairment due to the large fat mass surrounding their abdomen. PURPOSES: To examine the effect of the waist-to-hip (W/H) ratio on pulmonary gas exchange in the morbidly obese. METHODS: Twenty-five morbidly obese individuals (mean [+/- SD] age, 39 +/- 10 years; mean BMI, 49 +/- 7 kg/m2; mean body fat, 50 +/- 6%; mean waist circumference, 135 +/- 15 cm; mean W/H ratio, 0.97 +/- 0.11) scheduled for bariatric surgery were recruited. Arterial blood was sampled in duplicate after 5 min of rest sitting upright. RESULTS: The mean PaO2 at rest was 88 +/- 7 mm Hg (range, 72 to 108 mm Hg), the alveolar-arterial oxygen pressure difference (P[A-a]O2) was 19 +/- 9 mm Hg (range, 1 to 37 mm Hg), and the PacO2 was 38 +/- 3 mm Hg (range, 32 to 44 mm Hg). Linear regression showed that 32% and 36%, respectively, of the variance in the P(A-a)O2 and PaO2 were explained by the W/H ratio (p < 0.004 for both). As well, 20% of the variance in PacO2 was explained by the W/H ratio (p = 0.02). Men had larger W/H ratios (p < 0.01) and poorer gas exchange (p = 0.06) compared to women (mean difference: PaO2, -7 mm Hg; P[A-a]O2, 6 mm Hg). CONCLUSION: Morbidly obese men showed a trend to have poorer pulmonary gas exchange compared to morbidly obese women, and a significant part of the blood gas status in these patients is associated with the W/H ratio.

Ability of the human cytomegalovirus IE1 protein to modulate sumoylation of PML correlates with its functional activities in transcriptional regulation and infectivity in cultured fibroblast cells.

In one of the earliest events in human cytomegalovirus (HCMV)-infected cells, the major immediate-early (IE) protein IE1 initially targets to and then disrupts the nuclear structures known as PML oncogenic domains (PODs) or nuclear domain 10. Recent studies have suggested that modification of PML by SUMO is essential to form PODs and that IE1 both binds to PML and may disrupt PODs by preventing or removing SUMO adducts on PML. In this study, we showed that in contrast to herpes simplex virus type 1 (HSV-1) IE110 (ICP0), the loss of sumoylated forms of PML by cotransfected IE1 was resistant to the proteasome inhibitor MG132 and that IE1 did not reduce the level of unmodified PML. Reduced sumoylation of PML was also observed in U373 cells after infection with wild-type HCMV and proved to require IE1 protein expression. Mutational analysis revealed that the central hydrophobic domain of IE1, including Leu174, is required for both PML binding and loss of PML sumoylation and confirmed that all IE1 mutants tested that were deficient in these functions also failed both to target to PODs and to disrupt PODs. These same mutants were also inactive in several reporter gene transactivation assays and in inhibition of PML-mediated repression. Importantly, a viral DNA genome containing an IE1 gene with a deletion [IE1(Delta290-320)] that was defective in these activities was not infectious when transfected into permissive fibroblast cells, but the mutant IE1(K450R), which is defective in IE1 sumoylation, remained infectious. Our mutational analysis strengthens the idea that interference by IE1 with both the sumoylation of PML and its repressor activity requires a physical interaction with PML that also leads to disruption of PODs. These activities of IE1 also correlate with several unusual transcriptional transactivation functions of IE1 and may be requirements for efficient initiation of the lytic cycle in vivo.