Post-colectomy assessment of gastrointestinal function: a prospective study on colorectal cancer patients

Background

Anatomical changes after intestinal resection and the effects of adjuvant treatment for colorectal cancer may lead to gastrointestinal disturbances. The aim of our study was to assess gastrointestinal function using validated health-related quality of life (HRQoL) questionnaires that are able to reliably quantify patients’ symptoms.

Methods

Two hundred and eighty-nine colorectal cancer patients underwent HRQoL assessment preoperatively and at 3,6 and 12 months postoperatively. They were evaluated with the Gastrointestinal Quality of Life Index (GIQLI) [“global” and “symptoms” scales and questions 3 (“bloating”), 4 (“excessive gas”), 6 (“gurgling noises”), 7 (“frequent bowel movements (BMs)”), 30 (“urgent BMs”), 31 (“diarrhea”), 32 (“constipation”), 36 (“uncontrolled stools”)] and the European Organization for Research and Treatment of Cancer (EORTC) modules QLQ-C30 (symptom scales: “constipation” and “diarrhea”) and QLQ-CR29 (symptom scales: “defecation problems,” “incontinence,” and “bloating”).

Results

GIQLI “global” and “symptom” indices and the majority of single-item scores and the EORTC QLQ-C30 “constipation” and “diarrhea” subscales showed significant postoperative improvement (p < 0.05). Females and younger age (<70 years) patients appeared to have worse postoperative gastrointestinal function. Rectal cancer patients had more “urgent BMs,” “uncontrolled stools” and worse “global” and “symptom” scores at 3 months and more “diarrhea” at 3 and 6 months than colon cancer patients (p < 0.03). Right colectomy patients had less “excessive passage of gas,” “constipation,” and “uncontrolled stools” than left colectomy patients (3 months, p < 0.01). Anterior resection patients faced more gastrointestinal difficulties, especially in the first 6 months after surgery. Adverse effects related to stage and adjuvant treatment were predominant only at baseline (p < 0.05). GIQLI “diarrhea” and “constipation” scores were correlated with the respective EORTC QLQ-C30 domains (p = 0.0001).

Conclusions

Overall, gastrointestinal function is improved after colorectal cancer surgery. However, women and younger patients are at higher risk of postoperative gastrointestinal dysfunction.     

Randomized Pilot Study: Effects of an Exercise Programme and Leucine Supplementation in Patients with Cirrhosis

Background

Physical exercise could improve functional limitations, muscle mass, and health-related quality of life (HRQoL) in patients with cirrhosis.

Aim

The purpose of this study was to evaluate the efficacy and safety of an exercise programme and leucine supplementation to increase exercise capacity, muscle mass, and HRQoL in patients with cirrhosis.

Patients and Methods

Seventeen outpatients with cirrhosis were randomized to an exercise group (n = 8) or a control group (n = 9) in a pilot study. The programme of moderate exercise was performed for 12 weeks under supervision of a physiotherapist. All patients received oral leucine (10 g/day) during the study. At baseline and at the end of the study, we determined exercise capacity (6-min walk and 2-min step tests), anthropometric measurements, and HRQoL by Short Form-36 (SF-36) questionnaire. We also analyzed safety regarding complications of cirrhosis, liver and renal function, inflammatory response and oxidative stress.

Results

In the exercise group, exercise capacity improved, as shown by the increase in the 6-min walk test from 365 (160–420) to 445 m (250–500) (p = 0.01), and in the 2-min step test (p = 0.02). Lower thigh circumference also increased, from 41 (34–53) to 46 cm (36–56) (p = 0.02), and the domains of SF-36 general health (p = 0.03), vitality (p = 0.01) and social function (p = 0.04) improved significantly. In the control group, no statistically significant changes were observed in any of the parameters. We did not observe complications of cirrhosis in either group during the study.

Conclusions

A programme of moderate physical exercise together with leucine supplements in patients with cirrhosis is safe and improves exercise capacity, leg muscle mass and HRQoL.     

Sacral nerve stimulation for fecal incontinence improves symptoms, quality of life and patients' satisfaction: results of a monocentric series of 119 patients

Purpose

Sacral nerve stimulation (SNS) is validated as an efficient treatment for fecal incontinence (FI). However, long-term results are scarce in the literature. The goal of this study was to assess the impact of SNS on FI symptoms and quality of life, based on a retrospective analysis of prospectively collected data.

Methods

From 2001 to 2009, 119 patients (six men, mean age 61 years) underwent SNS testing for FI after an extensive diagnostic workup. Permanent implantation was realized when FI symptoms improved during testing, and follow-up visits were performed every 12 months thereafter. This follow-up evaluated morbidity and efficacy, based on clinical data and self-administered questionnaires including Jorge and Wexner FI score, urinary incontinence score (urinary distress inventory-6, UDI-6), gastrointestinal quality of life index (GIQLI), and auto-evaluation scale.

Results

A permanent stimulator was implanted after a positive test in 102 patients (91 %). Ten patients were explanted during follow-up (pain in one case and absence of efficacy in nine), and 29 had the stimulator and/or the electrode changed. The mean follow-up was 48 months (range 12–84): there was a significant improvement of FI score (9?±?1 vs 14?±?3, p?<?0.0001), UDI-6 score (8?±?4 vs 11?±?5, p?<?0.05), and GIQLI index (p?<?0.002). The improvement was present at 12 months follow-up and remained stable. Eighty percent of patients were satisfied with the treatment at the last point of follow-up. None of the pretreatment variables were predictive of SNS efficacy.

Conclusions

SNS improved FI and quality of life, and this efficacy remained over time. Although a complete disappearance of FI was rare, most patients were satisfied.     

Long-term quality of life after conservative treatment versus surgery for different stages of acute sigmoid diverticulitis

Purpose

It is controversial whether patients fare better with conservative or surgical treatment in certain stages of acute diverticulitis (AD), in particular when phlegmonous inflammation or covered micro- or macro-perforation are present. The aim of this study was to determine long-term quality of life (QoL) for AD patients who received either surgery or conservative treatment in different stages.

Methods

We included patients treated for AD at the University Hospital Grosshadern, Munich, Germany, between January 1, 2000, and December 31, 2010. Patients were classified by the Hansen and Stock (HS) classification, the modified Hinchey classification, and the German classification of diverticular disease (CDD). Pre-therapeutic staging was based on multidetector computed tomography. Long-term QoL was assessed by the Cleveland Global Quality of Life (CGQL) questionnaire, the Short Form 36 (SF-36), and the Gastrointestinal Quality of Life Index (GIQLI). Data are mean?±?SEM.

Results

Patients with phlegmonous AD (HS type 2a, Hinchey Ia and CDD 1b, respectively) had a better long-term QoL on the GIQLI when they were operated (78.5?±?2.5 vs. 70.7?±?2.1; p?<?0.05). Patients with micro-abscess (CDD 2a) had a better long-term QoL on the GIQLI, CGQL, and the “Role Physical” scale of the SF-36 when they were not operated (GIQLI 86.9?±?2.1 vs. 76.8?±?1.0; p?=?0.10; CGQL 82.8?±?5.1 vs. 65.3?±?11.0; p?=?0.08; SF-36/Role Physical 100?±?0.0 vs. 41.7?±?13.9; p?<?0.001). Patients with macro-abscess (CDD 2b) had a better long-term QoL when they were operated (GIQLI 89.3?±?1.4 vs. 69.5?±?4.5; p?<?0.01; CGQL 80.3?±?7.6 vs. 60.5?±?5.8; p?<?0.05; SF-36/Role Physical 95.8?±?4.2 vs. 47.9?±?13.6; p?<?0.001).

Conclusion

Considering long-term QoL, phlegmonous AD (HS type 2a, Hinchey Ia and CDD 1b, respectively) should be treated conservatively. In patients with covered perforation, abscess size should guide the decision on whether to perform surgery later on or not. In the light of long-term quality of life, patients fare better after elective sigmoid colectomy when abscess size exceeds 1 cm.

     

Sexual function and quality of life after surgical treatment for anal fistulas in Crohn’s disease

Background

The aim of this study was to assess sexual function and quality of life (QoL) in patients after surgery for perianal Crohn’s disease.

Methods

Eighty-eight consecutive patients with perianal Crohn’s disease, operated on at the Medical University of Vienna, completed a self-administered questionnaire including the International Index of Erectile Function (IIEF), Female Sexual Function Index (FSFI), Short Form-12 Health Survey (SF-12), and the Inflammatory Bowel Disease Questionnaire (IBDQ). Patients with a current stoma were excluded from further analysis. The median follow-up time was 104 months (range 3–186 months). Healthy subjects served as controls for each case and were matched by age (±6 years) and gender. Forty-seven (68 %) female and 22 male patients with a median age of 46.5 years (range 18–64 years) were analyzed. Eleven (16 %) patients had simple and 58 (84 %) complex anal fistulas.

Results

The median SF-12 physical health score of the patients was significantly lower (47.9 (range 25.5–57.2)) than that of the controls (54.3 (range 34.6–61.8); p = 0.03). Not surprisingly, the median total sore of the IBDQ of the controls was significantly better than that of the patients (controls: 188.5 (range 125–206.5), patients: 157 (range 60–199.5); p < 0.0001). Analysis with the multiple logistic regression test showed that type of operation, >1 perianal fistula opening, and active Crohn’s disease were independent risk factors for a worse IBDQ (p = 0.03, p = 0.015 and p < 0.0001). Interestingly, the median FSFI and IIEF score were not found to be significant different in any domain.

Conclusions

QoL but not sexual function is significantly influenced by surgery for perianal Crohn’s disease.     

A modified total colonic exclusion for elderly patients with severe slow transit constipation

Background

The aim of this study was to evaluate outcomes of total colonic exclusion with antiperistaltic ileorectal anastomosis (TCE-AIA) for elderly patients with slow transit constipation (STC).

Methods

Elderly patients (defined as age >65) who underwent TCE-AIA for severe idiopathic STC between 2009 and 2012 at our institution were identified. Postoperative outcomes and routine follow-up were assessed using the Wexner constipation score (WCS), gastrointestinal quality of life index (GIQLI) and four-point postoperative satisfaction scales.

Results

A total of 13 elderly patients were met the inclusion criteria. Five patients (38.5 %) were male, and eight patients (61.5 %) were female. The mean age of this population was 74 years (range 63–82 years). The mean operative time was 55 min (range 28–32), and blood loss was minimal. The mean postoperative hospital stay was 6.7 days (range 5–12 days). The mean time until the first postoperative bowel movement was 4 days (range 2–8 days). There was no procedure-related mortality and no major in-hospital complications. The median duration of follow-up was 12.4 months (range 6–29 months). None of the 13 patients had fecal incontinence or recurrence of constipation at the follow-up end point. However, eight patients underwent colonoscopy during follow-up, and four patients presented with diversion colitis. The patients’ preoperative WCS was 22.8 ± 3.3, and it had significantly improved to 5.4 ± 2.1 on 6 months after operation (p < 0.05). The preoperative GIQLI of 93.6 ± 20.5 had significantly increased to 120.8 ± 13.0 on 6 months after surgery (p < 0.05). Patient satisfaction at 6 months was very high in 11 patients and high in two patients.

Conclusions

TCE-AIA is a relatively simple procedure. It might be an effective surgical intervention for the selected elderly patients with STC.     

Consequences of Perceived Stigma Among Patients with Cirrhosis

Background

Among patients with diseases such as HIV, cancer and mental illness, perceived stigma is common and is linked to quality of life (QOL), depression and healthcare-seeking behavior.

Aims

We aimed to determine the prevalence and consequences of stigma in patients with cirrhosis.

Methods

A survey was developed and mailed to 300 patients with cirrhosis from a variety of etiologies. Among the 149 respondents, stigma was measured using a composite of previously validated scales. Correlates of stigma were measured using an a priori theoretical construct in order to investigate hypothesized consequences such as impaired social support, depression and reduction in healthcare-seeking behavior.

Results

Eighty-nine percent of respondents chose “agree” or “strongly agree” for at least one of the 18 stigma-related questions, indicating they felt stigmatized in at least one aspect of their lives. Patient factors associated with more perceived stigma on multivariable linear regression included younger age (p = 0.008), and hepatitis C (p = 0.001) or alcohol (p = 0.01) as the etiology of liver disease. Patients with higher levels of perceived stigma had less social support (r ² = 0.898, p < 0.001), were less likely to seek medical care (r ² = 0.108, p < 0.001), suffered from more depression (r ² = 0.17 p < 0.001) and had worse QOL (r ² = 0.175, p < 0.001).

Conclusions

Perceived stigma is common among patients with cirrhosis, and is associated with adverse attitudes and behaviors such as decreased healthcare-seeking behavior. Healthcare providers need to be aware of these perceptions and their potential impact on patients’ interaction with the medical system.     

Sacral neuromodulation for fecal incontinence and “low anterior resection syndrome” following neoadjuvant therapy for rectal cancer

Background

It was the aim of this prospective study to analyze both feasibility and effectiveness of sacral neuromodulation for fecal incontinence and “low anterior resection syndrome” following neoadjuvant therapy for rectal cancer.

Methods

All patients who underwent sacral neuromdulation following neoadjuvant therapy for rectal cancer (preoperative radiochemotherapy, oncologic rectal resection with total mesorectal excision) were prospectively enrolled in the study. Only patients with failure of conservative treatment and without any evidence of residual or recurrent tumor disease were candidates for sacral neuromdulation which was performed by a two-stage procedure (diagnostic percutaneous test stimulation followed by definite implant). In addition to feasibility, primary end points included success (reduction of incontinent episodes), continence and defecation status (assessed by Cleveland Clinic Incontinence Score and Altomare score), and quality of life (EQ-5D). Anal manometry was performed preoperative and at 12-month follow-up. Follow-up information was derived from clinical examination 3, 6, and 12 months postoperatively.

Results

Nine patients (three females, six males) with a mean age of 61 years underwent sacral neuromodulation following neoadjuvant therapy for rectal cancer. Implantation rate was 100 %. No septic morbidity was observed. After a mean follow-up of 12 months, mean Cleveland Clinic Incontinence Score was reduced from 18.2 to 6.0 (p?<?0.01). Incontinence episodes were significantly reduced from 7 to 0.5 (per day) and 20 to 8 (per week). Fecal urgency, fragmented defecation, and soiling were improved or resolved in two thirds. Altomare score was significantly reduced from 21.0 to 9.3 (p?<?0.01). Anorectal manometry did not correlate with clinical success. Quality of life was significantly improved (EQ-5D generic: 0.42 vs. 0.74, EQ-5D-VAS score: 20 vs. 90, p?<?0.01).

Conclusions

Preliminary results of sacral neuromodulation in patients with fecal incontinence and symptoms of “low anterior resection syndrome” are promising and enrich the therapeutic modalities if conservative management has failed.     

Breast Cancer Treatment Decision-Making: Are We Asking Too Much of Patients?

OBJECTIVE

Physicians are mandated to offer treatment choices to patients, yet not all patients may want the responsibility that entails. We evaluated predisposing factors for, and long-term consequences of, too much and not enough perceived decision-making responsibility among breast cancer patients.

DESIGN

Longitudinal assessment, with measurements collected just after surgical treatment (baseline) and 6-month follow-up.

PARTICIPANTS

Women with early-stage breast cancer treated surgically at eight NYC hospitals, recruited for a randomized controlled trial of patient assistance to improve receipt of adjuvant treatment.

MEASUREMENTS

Using logistic regression, we explored multivariable-adjusted associations between perceived treatment decision-making responsibility and a) baseline knowledge of treatment benefit and b) 6-month decision regret.

RESULTS

Of 368 women aged 28–89 years, 72 % reported a “reasonable amount”, 21 % “too much”, and 7 % “not enough” responsibility for treatment decision-making at baseline. Health literacy problems were most common among those with “not enough” (68 %) and “too much” responsibility (62 %). Only 29 % of women had knowledge of treatment benefits; 40 % experienced 6-month decision regret. In multivariable analysis, women reporting “too much” vs. “reasonable amount” of responsibility had less treatment knowledge ([OR] = 0.44, [95 % CI] = 0.20–0.99; model c?=?0.7343;p?<?0.01) and more decision regret ([OR] = 2.,91 [95 % CI] = 1.40–6.06; model c?=?0.7937;p?<?0.001). Findings were similar for women reporting “not enough” responsibility, though not statistically significant.

CONCLUSION

Too much perceived responsibility for breast cancer treatment decisions was associated with poor baseline treatment knowledge and 6-month decision regret. Health literacy problems were common, suggesting that health care professionals find alternative ways to communicate with low health literacy patients, enabling them to assume the desired amount of decision-making responsibility, thereby reducing decision regret.     

Impact of BMI on serum estradiol and bone turnover markers in postmenopausal women with hormone-sensitive early breast cancer treated with anastrozole

Purpose

Obesity increases the risk of all-cause and breast cancer mortality. As obese patients have higher levels of aromatase enzyme activity, conflicting results on the effect of body mass index (BMI) of a standard dose aromatase inhibitor on estradiol depletion have been reported.

Methods

We prospectively investigated the effect of BMI on the efficacy of anastrozole in 70 postmenopausal women with early, ER-positive breast cancer to decrease serum estradiol assessed by a high-sensitive assay with a sensitivity limit of 5 pg/ml over 24 months. Additionally, we examined the changes of bone markers expecting an inverse relationship.

Results

Overall, estradiol decreased from 12.6 pg/ml (SD = 5.4) to 4.0 pg/ml (SD = 5.6) over 24 months (p < 0.001). In contrast, carboxy-terminal collagen crosslinks (CTX) and serum aminoterminal propeptide of type I collagen (PINP) increased from 0.26 ng/ml (SD = 0.18) to 0.40 ng/ml (SD = 0.24) and 41.5 ng/ml (SD = 19.7) to 59.1 ng/ml (SD = 29.1) (p < 0.0001 for both). Baseline estradiol comprised significant differences comparing normal weight with overweight (p < 0.01) or obese patients (p < 0.001). After 12 and 24 months, overweight and obese patients showed a slightly, but insignificantly higher concentrations of estradiol compared to normal weight subjects. We found differences of CTX in comparison between normal weight and obese patients (0.33 vs. 0.21 ng/ml; p < 0.023) at baseline. At 12 and 24 months, there was a significant BMI-independent increase in CTX.

Conclusions

Estradiol concentrations in postmenopausal women with early, ER-positive breast cancer on anastrozole were significantly different in normal weight versus overweight or obese patients at baseline, but not at 12 and 24 months. CTX and PINP present a notable increase in the first 12 months of anastrozole treatment, stabilizing thereafter.     

Improvement of health status evaluated by Arthritis Impact Measurement Scale 2 (AIMS-2) and Short Form-36 (SF-36) in patients with rheumatoid arthritis treated with tocilizumab

Objective

To evaluate the improvement of health status in patients with rheumatoid arthritis (RA) treated with tocilizumab.

Methods

Thirty-nine patients were treated with 8 mg/kg tocilizumab every 4 weeks for 24 weeks. Disease activity was assessed by Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI). Improvement of health status was assessed by Arthritis Impact Measurement Scale 2 (AIMS-2) and Short Form-36 (SF-36).

Results

Tocilizumab improved CDAI and SDAI significantly at week 4 compared with at baseline. In the components of AIMS-2, “physical score”, “symptom” and “affect” improved significantly at week 4 compared with at baseline, while “social interaction” did not improve significantly during 24 weeks of tocilizumab therapy. Similarly in SF-36, “bodily pain”, “general health”, “vitality” and “mental health” improved significantly at week 4. The most correlative component of AIMS-2 with CDAI was “symptom”, while “social interaction” did not correlate with CDAI during tocilizumab treatment.

Conclusion

The time-course diversity in improvement of health status should be considered to provide proper healthcare when treated with tocilizumab.     

Hemorrhoidal dearterialization with mucopexy versus hemorrhoidectomy: 3-year follow-up assessment of a randomized controlled trial

Background

A randomized controlled trial showed that patients with grade III or IV internal hemorrhoids had similar symptomatic relief of symptoms up to 3 months following dearterialization with mucopexy or hemorrhoidectomy albeit with less postoperative pain after the former. This study aimed to compare hemorrhoidal recurrence and chronic complications at 3-year follow-up.

Methods

This study was carried out on 40 patients with grade III or IV internal hemorrhoids previously enrolled to a randomized trial comparing dearterialization to hemorrhoidectomy. Recurrence was defined as internal hemorrhoids diagnosed on proctoscopy. Chronic complications were nonresolving adverse events related to surgery. Outcome measures included patient-reported outcomes and quality of life measured by brief pain inventory (BPI), SF-12, and fecal incontinence surveys.

Results

At median follow-up of 36 (27–43) months, 13 patients (32.5 %) were lost to follow-up. Patient-reported outcomes suggested no difference between dearterialization and hemorrhoidectomy in persistent symptoms, occurring in 1 (8.3 %) vs. 2 (13.3 %) patients (p = 0.681) and in symptom recurrence, occurring in 6 (50 %) vs. 4 (26.7 %) patients (p = 0.212). On proctoscopy, recurrence was seen in 2 (13.3 %) vs. 1 (6.7 %) patients (p = 0.411), all with index grade IV disease. One patient in each arm required reoperation (p = 0.869). Chronic complications were not seen in the dearterialization arm while they occurred in 2 (13.3 %) hemorrhoidectomy patients (p = 0.189) and included unhealed wound (n = 1), anal fissure (n = 1) and fecal incontinence (n = 1). There was a trend toward more patient reported than actual recurrence on proctoscopy (10 vs. 3, p = 0.259). There was no difference in BPI, SF-12, and fecal incontinence quality of life scores.

Conclusions

Recurrence rates did not differ significantly at 3-year follow-up and occurred in patients with index grade IV hemorrhoids. Chronic complications occurred only after hemorrhoidectomy.     

Aspirin Dose Increase from 75 to 150 mg Suppresses Red Blood Cell Contribution to Suboptimal Platelet Response to Aspirin in Patients with CAD

Purpose

To verify the hypothesis that erythrocytes play a role in suboptimal blood platelet response to acetylsalicylic acid (ASA, aspirin) in subjects with coronary artery disease (CAD).

Methods

In a cross-over randomized controlled intervention study we evaluated blood platelet response to 30-day treatment with 75 mg/d or 150 mg/d of ASA (enteric coated) in CAD patients (n?=?125). In vitro platelet response to collagen or arachidonic acid was monitored with impedance aggregometry and plasma thromboxane B₂ was assayed immunoenzymatically. Blood morphology and several plasma biochemical parameters were determined using routine diagnostic procedures.

Results

CAD patients demonstrated lower blood platelet responsiveness to 75 mg/d of ASA compared to healthy subjects. The improved platelet responsiveness to 150 mg/d of ASA was particularly evident in “poor” responding patients. Positive correlations between platelet “poor” response to lower (75 mg/d) ASA dose and red blood cell count (R_s?=?0.215; p?<?0.04), haemoglobin (R_s?=?0.232; p?<?0.02) and haematocrit (R_s?=?0.239; p?<?0.02) were found in CAD patients. Association between “poor” platelet response with lower ASA dose was confirmed by conditional maximum likelihood logistic regression, which showed the independency between erythrocyte-derived parameters, as the risk factors for suboptimal platelet response to ASA, and other risk factors, like CRP or LDL-cholesterol. In “poor” ASA responders taking the higher ASA dose (150 mg/d) the correlation between platelets’ response to ASA and erythrocyte-derived parameters was not significant.

Conclusions

Red blood cell parameters are associated with suboptimal blood platelet response to ASA in patients with CAD. Such a platelet refractoriness to ASA may be effectively overcome by increasing the ASA dose.     

Modulation of peripheral immune responses by paclitaxel–ifosfamide–cisplatin chemotherapy in advanced non-small-cell lung cancer

Purpose

The aim of this study was to assess systemic immunological responses in non-small-cell lung cancer (NSCLC) patients with stage III/IV disease during treatment with paclitaxel–ifosfamide–cisplatin (TIP) chemotherapy.

Methods

Peripheral blood mononuclear cells (PBMCs) collected from healthy donors (HD) (n = 20) and chemotherapy-naive NSCLC patients treated with TIP (n = 32) were tested for production of IL-1, TNF-α, TNF-β, IL-6, IL-8, IL-10, IL-12 and IL-2 upon polyclonal stimulation with anti-CD3 mAb. They were further assessed over a treatment period of twelve weeks (i.e., four treatment cycles).

Results

PBMCs from NSCLC patients produced higher IL-1, TNF-α, TNF-β, IL-6, IL-8, IL-10 and IL-12 levels, whereas IL-2 exhibited lower values compared to HD (p < 0.001 for all parameters). Of interest, patients who responded to treatment had significantly higher increases in IL-2 (p < 0.001) and significantly higher decreases in IL-1 (p < 0.001), TNF-α (p < 0.001), TNF-β (p < 0.001), IL-6 (p = 0.02), IL-8 (p < 0.001), IL-10 (p < 0.001) and IL-12 (p < 0.001) levels. Non-responders revealed post-therapeutically a significantly higher increase in IL-1, TNF-α, TNF-β, IL-6, IL-8, IL-10 and IL-12 secretion and a significantly higher decrease in IL-2 levels (p < 0.001 for all parameters). Patients who responded to treatment and had a significantly higher increase in IL-2 showed a significantly longer median survival (p value < 0.001, 26 vs. 7.5 months).

Conclusion

Our study indicates that monitoring cytokine dynamics in patients with advanced NSCLC and especially those of IL-2 in peripheral blood components in vitro could be used as a predictor of treatment-related outcome and overall survival in NSCLC.     

Surgical outcome and prognostic factors after treatment of osteoradionecrosis of the jaws

Purpose

This prospective study attempts to identify prognostic factors for outcome in patients Classes 2 and 3 osteoradionecrosis (ORN) treated using individualized methods.

Methods

From 2005 to 2010, patients with Classes 2 and 3 osteoradionecrosis of the jaws were treated by the same surgical team using standard protocols. The patients were evaluated prospectively and followed up for a minimum of 12 months after completion of treatment. Two examinations were performed at least six months apart.

Results

A total of 94 patients were assessed. Local debridement was performed in 33 patients (35.1 %), a rim resection with the application of a reconstruction plate was performed in 35 patients (37.2 %), and continuity resection in 26 patients (27.7 %). Postoperative wound infections locally or at the neck were detected in 69 patients (70.2 %), failure to eradicate radionecrosis occurred in 50 patients (53.2 %). The location of the primary tumor (p = 0.023) and radiation dose (p = 0.049), were associated with a significant risk of development of ORN. Prognostic factors for failure of treatment were the extent of initial osteoradionecrosis (p = 0.049) surgical treatment (p < 0.0001), number of debridements (p < 0.0001), type of microvascular free flap with (p < 0.0001), and grossly infected ORN (p < 0.0001).

Conclusions

Several factors affect the outcome of treatment of ORN. We confirm many of the intuitive factors influence outcome of treatment and add evidence that complete removal of affected bone and watertight well vascularized coverage is the most useful treatment strategy.     

Magnifying narrow-band imaging of surface maturation in early differentiated-type gastric cancers after Helicobacter pylori eradication

Background

Even after successful Helicobacter pylori eradication, primary or metachronous gastric cancers are sometimes discovered. The endoscopic features of these cancers may be modified by controlling inflammation. Characteristic findings for such lesions in terms of narrow-band imaging with magnifying endoscopy (NBI-ME) and histopathology need to be clarified to allow accurate diagnosis.

Methods

Distinctive NBI-ME characteristics were examined retrospectively in intramucosal or minimally submucosal and differentiated-type adenocarcinomas from a successful eradication group (42 patients, 50 lesions) and a non-eradicated control group (44 patients, 50 lesions) matched in age and sex. A “gastritis-like” appearance under NBI-ME was characterized by uniform papillae and/or tubular pits with a whitish border, regular or faint microvessels and unclear demarcation, resembling the adjacent noncancerous mucosa. Histological differentiation at the luminal surface of the cancer was evaluated according to Ki-67 immunoreactivity restricted at the middle or lower portion of the tubules. NBI-ME alteration was prospectively confirmed in 29 patients (30 lesions) after eradication therapy.

Results

The frequency of a “gastritis-like” appearance was 44 % (22/50) for the eradication group, which was significantly higher than the 4 % (2/50) for the control group (p < 0.001). In the eradication group, the “gastritis-like” appearance was significantly correlated with histological surface differentiation (p < 0.001). In the prospective study, NBI-ME showed changes to heterogeneous papillary microstructures in 43 % (10/23) of the lesions after successful eradication at short-term follow-up.

Conclusions

Identification of surface maturation under NBI-ME offers a promising approach for accurate diagnosis of early gastric cancers after successful eradication.     

Telmisartan Plus Propranolol Improves Liver Fibrosis and Bile Duct Proliferation in the PSC-Like Abcb4−/− Mouse Model

Background

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease leading to cirrhosis and cholangiocellular carcinoma. Inhibitors of the renin–angiotensin system or the sympathetic nervous system delay liver fibrogenesis in animal models.

Aims

We investigated the antifibrotic potential of telmisartan, an angiotensin II type 1 receptor antagonist, and the β-adrenoceptor blocker propranolol in the PSC-like Abcb4 knockout mouse model.

Methods

Sixty-five Abcb4 ^?/? mice were treated with telmisartan for 3 or 5 months (T) and with telmisartan plus propranolol for 3, 5, or 8 months (TP), or for 2 or 5 months starting with a delay of 3 months (TP delayed). Liver hydroxyproline content, inflammation, fibrosis, and bile duct proliferation were assessed; fibrosis-related molecules were analyzed by real-time polymerase chain reaction and Western blotting.

Results

Compared to controls, telmisartan monotherapy had no significant influence on hydroxyproline; however, telmisartan plus propranolol reduced hydroxyproline (TP 3 months, p = 0.008), fibrosis score (TP 3 months and TP 8 months, p = 0.043 and p = 0.008, respectively; TP delayed 8 months, p < 0.0005), bile duct proliferation (TP 8 months and TP delayed 8 months, p = 0.006 and p < 0.0005, respectively), and procollagen α1(I), endothelin-1, TIMP-1 and MMP3 mRNA as well as α-SMA, CK-19, and TIMP-1 protein.

Conclusions

Telmisartan plus propranolol reduces liver fibrosis and bile duct proliferation in the PSC-like Abcb4 ^?/? mouse model, even when started at late stages of fibrosis, and may thus represent a novel therapeutic option for cholestatic liver diseases such as PSC.     

Laparoscopic ventral rectopexy: a prospective long-term evaluation of functional results and quality of life

Background

Laparoscopic ventral rectopexy for rectal prolapse combines the advantages of a minimally invasive approach with the low recurrence rate observed after abdominal procedures. To date, only a few long-term functional studies and no quality of life assessment are available. The aim of this study was to assess long-term functional outcomes and quality of life after laparoscopic ventral rectopexy.

Methods

Between January 2007 and December 2008, patients who underwent laparoscopic ventral rectopexy for full-thickness external rectal prolapse and/or rectocele were prospectively included. Fecal incontinence and constipation were scored (Wexner score and Rome II criteria). Quality of life was assessed using the gastrointestinal quality of life form (GIQLI).

Results

Thirty-three patients were included and 30 (91 %) completed all the questionnaires. There was no morbidity or mortality. The mean length of hospital stay was 5 ± 1 days (range 3–7 days). After a mean follow-up of 42 ± 7 months (range 32–52 months), recurrence of rectocele was observed in two patients (6 %). At the end of follow-up, constipation was improved in 13/18 patients (72 %) and two patients (7 %) presented de novo constipation. The patients’ Wexner score improved between preoperative status and end of follow-up (12 ± 7 vs. 4 ± 3, p = 0.002). Compared to the preoperative score, quality of life significantly improved over time: 77 ± 21 preoperatively versus 107 ± 17 at 1 year versus 109 ± 18 at the end of follow-up (p < 0.001).

Conclusions

This prospective study showed that laparoscopic ventral rectopexy was associated with excellent postoperative outcomes and a low long-term recurrence rate. Long-term functional results were excellent in terms of continence, with significant improvement of quality of life and without worsening constipation.     

Enzyme replacement therapy for alpha-mannosidosis: 12 months follow-up of a single centre, randomised, multiple dose study

Background

Alpha-mannosidosis (OMIM 248500) is a rare lysosomal storage disease (LSD) caused by alpha-mannosidase deficiency. Manifestations include intellectual disabilities, facial characteristics and hearing impairment. A recombinant human alpha-mannosidase (rhLAMAN) has been developed for weekly intravenous enzyme replacement therapy (ERT). We present the preliminary data after 12 months of treatment.

Methods

This is a phase I-II study to evaluate safety and efficacy of rhLAMAN. Ten patients (7–17 y) were treated. We investigated efficacy by testing motor function (6-minutes-Walk-Test (6-MWT), 3-min-Stair-Climb-Test (3-MSCT), The Bruininks-Oseretsky Test of Motor Proficiency (BOT2), cognitive function (Leiter-R), oligosaccharides in serum, urine and CSF and Tau- and GFA-protein in CSF.

Results

Oligosaccharides: S-, U- and CSF-oligosaccharides decreased 88.6 % (CI ?92.0 ?85.2, p?<?0.001), 54.1 % (CI ?69.5- ?38.7, p?<?0,001), and 25.7 % (CI ?44.3- ?7.1, p?<?0.05), respectively. Biomarkers: CSF-Tau- and GFA-protein decreased 15 %, p?<?0.009) and 32.5, p?<?0.001 respectively. Motor function: Improvements in 3MSCT (31 steps (CI 6.8-40.5, p?<?0.01) and in 6MWT (60.4 m (CI ?8.9 ?51.1, NS) were achieved. Cognitive function: Improvement in the total Equivalence Age of 4 months (0.34) was achieved in the Leiter R test (CI ?0.2-0.8, NS).

Conclusions

These data suggest that rhLAMAN may be an encouraging new treatment for patients with alpha-mannosidosis.The study is designed to continue for a total of 18 months. Longer-term follow-up of patients in this study and the future placebo-controlled phase 3 trial are needed to provide greater support for the findings in this study.     

Disability is the major negative predictor for achievement of Boolean-based remission in patients with rheumatoid arthritis treated with tocilizumab

Objective

To analyze the efficacy of tocilizumab (TCZ) and the factors that influence achievement of Boolean-based remission in patients with rheumatoid arthritis (RA) treated with TCZ in daily clinical practice.

Methods

The efficacy of TCZ at 24 weeks after initiation of TCZ in 80 patients with RA was analyzed by comparing achievement of “DAS28 remission” with that of “Boolean-based remission”. The predictive factors that influence achievement of Boolean-based remission were determined using multiple logistic regression analysis using a step-wise method.

Results

DAS28 remission and Boolean-based remission were achieved in 50.0 and 12.5 % of patients, respectively. Significant differences in achieving Boolean-based remission were observed when patients were stratified by disease duration in tertiles (p < 0.05) and by physical function in tertiles (p < 0.05); no such differences were observed for achieving DAS28 remission. The least achievable component among the Boolean-based remission criteria was patient’s global assessment. The predictive factor for not achieving Boolean-based remission at 24 weeks was having a worse baseline physical function (odds ratio, 3.66; 95 % confidence interval, 1.17–14.48).

Conclusions

This study suggests that baseline disability predicts a lack of achievement of Boolean-based remission. Thus, better responses to TCZ may be obtained when TCZ is initiated in RA patients before disability develops.