Patient-reported sexual toxicity after radiation therapy in long-term prostate cancer survivors.

BACKGROUND: To present an overview of patient-reported sexual toxicity in sexually active long-term prostate cancer survivors treated with radiation therapy. METHODS: We used patient-reported outcomes from a study-specific questionnaire surveying symptoms after prostate cancer radiation therapy. Data from 518 men treated at the Sahlgrenska University Hospital in Sweden from 1993 to 2006 were analysed. The men had undergone primary or salvage external beam radiation therapy (EBRT) or EBRT combined with high-dose rate brachytherapy (BT). We also used information from 155 non-treated reference men from the general population with no history of prostate cancer, matched for age and residency. RESULTS: Median time from treatment to follow-up was 5 years (range: 1-14 years). Among the 16 investigated symptoms on erectile function, libido, orgasm, and seminal fluid, 9 symptoms in the primary EBRT group and 10 in both the salvage EBRT and the EBRT+BT groups were statistically significantly more prevalent in survivors than in reference men. Erectile dysfunction was influenced by both age and time to follow-up, whereas symptoms relating to orgasm and seminal fluid were influenced by time to follow-up only. Not being sexually active was almost one and a half times as common in survivors as in reference men. CONCLUSIONS: The presented symptom profiles can help to develop personalized therapy for prostate cancer through a better understanding of which radiation-induced toxicities to be addressed in the clinic and can also assist in identifying suitable interventions for existing symptoms.

Decreased Rates of Radiation-induced Trismus and Lowered Mastication Structure Doses in Patients Treated for Head and Neck Cancer During the Last Two Decades.

AIMS: To investigate how absorbed doses to mastication structures in modern radiotherapy (RT) technique for head and neck cancer (HNC) compared with earlier RT techniques and with published trismus tolerance doses. To compare the incidence of radiation-induced trismus by earlier and newer RT techniques. MATERIALS AND METHODS: This study investigated two HNC patient cohorts treated with RT in 2007-2012 (three-dimensional conformal radiotherapy [3DCRT] and/or intensity-modulated radiotherapy [IMRT]; n =121 [Cohort 1]) and 2017-2020 (volumetric-modulated arc therapy [VMAT]; n =124 [Cohort 2]). All patients underwent RT without mastication structure-sparing intent, had normal mouth-opening ability before RT, and were prospectively assessed. Trismus was defined as the maximal interincisal opening ≤35 mm at any follow-up (3-, 6-, and 12-months post-RT). The temporomandibular joints (TMJs), masseter, and medial/lateral pterygoid muscles were delineated on the planning CT:s. Mean doses were compared between cohorts, and evaluated with respect to published trismus tolerance doses. P values ≤ 0.05 indicated statistical significance. RESULTS: Within 12 months post RT, 74/121 (61%) of patients in Cohort 1 had experienced trismus compared to 11/124 (9%) in Cohort 2. Averaged mean doses (±S.D.) for the masseter muscles were 35.2±8.3 Gy in Cohort 1 and 20.2±8.7 Gy in Cohort 2 (P <0.001). Corresponding numbers were 19.1±16.2 and 4.3±4.3 Gy for the TMJs, 53.7±10.1 and 40.2±16.8 Gy for the medial pterygoid muscles, and 29.2±18.7 and 9.2±8.4 Gy for the lateral pterygoid muscles (all P <0.001). Masseter muscle doses were below tolerance doses in 23% of patients in Cohort 1 compared with 90% in Cohort 2. The corresponding numbers were 52% and 96% for the TMJs, 8% and 36% for the medial pterygoid muscles and 72% and 100% for the lateral pterygoid muscles. CONCLUSION: Mastication structure mean doses by more recent RT techniques were generally below proposed tolerance doses, with dose reductions of 10-20 Gy compared with earlier techniques. Modern RT without mastication-structure-sparing intent resulted in below 10% of HNC patients experiencing trismus compared with 60% treated with earlier techniques.

Patient-reported genitourinary toxicity for long-term prostate cancer survivors treated with radiation therapy.

BACKGROUND: The objective of this study is to provide comprehensive overviews of patient-reported urinary symptoms for long-term prostate cancer survivors treated with radiation therapy and for untreated, healthy men. METHODS: We performed a population-based cross-sectional study using a study-specific postal questionnaire assessing symptoms among 1007 men consecutively treated at the Sahlgrenska University Hospital, Göteborg, Sweden from 1993-2006 (primary or salvage external beam radiation therapy (EBRT) or EBRT and high-dose rate brachytherapy). We also randomly recruited 350 non-pelvic-irradiated matched control men from the Swedish Total Population Register. Symptom prevalence and prevalence ratios were computed. RESULTS: Survey participation rate was 89% (874/985) for eligible survivors and 73% (243/332) for eligible controls. Median time from treatment to follow-up was 5 years (range, 1-14 years). Among the 21 investigated symptoms reflecting obstruction, frequency, urgency, pain and incontinence, we found significantly higher prevalence compared with controls for 9 symptoms in the EBRT group, 10 in the EBRT+brachytherapy group and 5 in the salvage EBRT group. The prevalence for a majority of the symptoms was stable over time. CONCLUSION: The presented toxicity profiles provide a thorough understanding of patient-reported urinary symptoms that can assist in developing personalised therapy for prostate cancer.

Effects of lung tissue characterization in radiotherapy of breast cancer under deep inspiration breath hold when using Monte Carlo dosimetry.

PURPOSE: To investigate the sensitivity of Monte Carlo (MC) calculated lung dose distributions to lung tissue characterization in external beam radiotherapy of breast cancer under Deep Inspiration Breath Hold (DIBH). METHODS: EGSnrc based MC software was employed. Mean lung densities for one hundred patients were analysed. CT number frequency and clinical dose distributions were calculated for 15 patients with mean lung density below 0.14 g/cm3. Lung volume with a pre-defined CT numbers was also considered. Lung tissue was characterized by applying different CT calibrations in the low-density region and air-lung tissue thresholds. Dose impact was estimated by Dose Volume Histogram (DVH) parameters. RESULTS: Mean lung densities below 0.14 g/cm3 were found in 10% of the patients. CT numbers below -960 HU dominated the CT frequency distributions with a high rate of CT numbers at -990 HU. Mass density conversion approach influenced the DVH shape. V4Gy and V8Gy varied by 7% and 5% for the selected patients and by 9% and 3.5% for the pre-defined lung volume. V16Gy and V20Gy, were within 2.5%. Regions above 20 Gy were affected. Variations in air- lung tissue differentiation resulted in DVH parameters within 1%. Threshold at -990 HU was confirmed by the CT number frequency distributions. CONCLUSIONS: Lung dose distributions were more sensitive to variations in the CT calibration curve below lung (inhale) density than to air-lung tissue differentiation. Low dose regions were mostly affected. The dosimetry effects were found to be potentially important to 10% of the patients treated under DIBH.

Salvage radiation therapy in prostate cancer: relationship between rectal dose and long-term, self-reported rectal bleeding.

PURPOSE: To quantify the relationship between the rectal dose distribution and the prevalence of self-reported rectal bleeding among men treated with salvage radiotherapy (ST) delivered by three-dimensional conformal radiotherapy (3DCRT) for prostate cancer. To use this relationship to estimate the risk of rectal bleeding for a contemporary cohort of patients treated with volumetric modulated arc therapy (VMAT) ST. METHODS AND PATIENTS: Rectal bleeding of any grade was reported by 56 (22%) of 255 men in a PROM-survey at a median follow-up of 6.7 years after 3DCRT ST. Treatment plan data were extracted and dose-response relationships for the rectal volumes receiving at least 35 Gy (V35Gy) or 63 Gy (V63Gy) were calculated with logistic regression. These relationships were used to estimate the risk of rectal bleeding for a cohort of 253 patients treated with VMAT ST. RESULTS: In the dose-response analysis of patients in the 3DCRT ST cohort, both rectal V35Gy and V63Gy were statistically significant parameters in univariable analysis (p = 0.005 and 0.003, respectively). For the dose-response models using either rectal V35Gy or V63Gy, the average calculated risk of rectal bleeding was 14% among men treated with VMAT ST compared to a reported prevalence of 22% for men treated with 3DCRT ST. CONCLUSIONS: We identified dose-response relationships between the rectal dose distribution and the risk of self-reported rectal bleeding of any grade in a long-term perspective for men treated with 3DCRT ST. Furthermore, VMAT ST may have the potential to decrease the prevalence of late rectal bleeding.

Small intestinal mucin antigen (SIMA); a novel tumour marker in colorectal cancer?

The aim of the present prospective study was to evaluate the clinical value of a new serum tumour marker small intestinal mucin antigen (SIMA) in the diagnosis of colorectal cancer. The serum SIMA values were measured in a prospective series of patients with colorectal cancer (n = 73) and patients with benign gastrointestinal disease (n = 87). SIMA values were determined using two different techniques. The cut-off levels (90 % specificity) determined for each test were 12.0 U/ml for SIMA I (Delphia), 9.8 U/ml for SIMA II (PCA-Delphia), 2.5 ng/ml for CEA, 17 U/ml for CA 50 and 17 U/ml for CA 242. The diagnostic sensitivity of the SIMA I test was 0.27, of the SIMA II test it was 0.19, of the CEA test it was 0.63, of the CA 50 test it was 0.30 and 0.30 for the CA 242 test in detecting colorectal cancer. The correlation coefficients (Pearson's r) in colorectal cancer patients between SIMA I and SIMA II measurements were 0.99, 0.71 between CEA and CA 50, 0.70 between CEA and CA 242 and 0.96 between CA 50 and CA 242 measurements. The correlation coefficients in colorectal cancer patients between other serum markers were non-significant. All marker tests were entered in a multivariate analysis to find the best combination of independent predictors of colorectal cancer. The most important predictor of colorectal cancer was SIMA I. In order to calculate the contributions of tumour marker tests, a diagnostic score (DS) was developed. The sensitivity of the DS in detecting colorectal cancer was 0.33 with a specificity of 0.90 and an efficiency of 0.65. In conclusion, the results indicate that the diagnostic sensitivity of a new tumour marker SIMA is equal to CA50 and CA 242, but inferior to the diagnostic sensitivity of the CEA test. However, multivariate discriminant analysis suggests some diagnostic value for SIMA I test because of its independent discriminant value.

High-dose ropivacaine wound infiltration for pain relief after inguinal hernia repair: a clinical and pharmacokinetic evaluation.

BACKGROUND AND OBJECTIVES: Early data on ropivacaine, a recently introduced local anesthetic, indicate a longer duration of skin analgesia than with bupivacaine, along with lower toxicity. The objective of this study was to evaluate ropivacaine 7.5 mg/mL for wound infiltration pain relief after hernia surgery, in higher doses than used before, in an open, nonrandomized design. METHODS: Twenty otherwise healthy men underwent elective unilateral open hernia repair by the same surgeon. General anesthesia was used during surgery, and infiltration of the operating field with 300 mg (n = 10) or 375 mg (n = 10) ropivacaine, 7.5 mg/mL, was employed for postoperative pain relief. Any sign of an adverse event was recorded. Plasma concentrations of ropivacaine were monitored. Pain at rest and on mobilization was regularly assessed over 24 hours by a visual analog scale. Patients' ability to walk and void and the need for supplementary analgesics were recorded. RESULTS: No serious adverse effects occurred. Plasma concentrations showed large variations but no toxic levels. No significant differences between the two groups were detected in pain scores which were low in both groups, at rest or on mobilization, or in the consumption of supplementary analgesics. At 4 hours, 19 patients were able to walk. Within 8 hours of surgery, all patients had passed urine without any problem. Wound healing was normal. CONCLUSIONS: Infiltration of ropivacaine 7.5 mg/mL during hernia surgery can be employed safely in doses of 300 mg and 375 mg to control pain after hernia surgery. The lower dose is recommended, since the higher one did not give any clinically relevant advantages.

Pain relief by wound infiltration with bupivacaine or high-dose ropivacaine after inguinal hernia repair.

BACKGROUND AND OBJECTIVES: Wound infiltration with bupivacaine is often used for pain relief after inguinal hernia surgery. We hypothesized that the lower systemic toxicity of another long-acting local anesthetic of similar potency (ropivacaine) would make it possible to increase the dose to above that recommended for bupivacaine and thereby achieve more effective pain control. METHODS: Elective unilateral open hernia repair was performed on 144 patients at 4 hospitals. Surgery was performed under general anesthesia and, in a double-blind manner, the operating field was infiltrated with 40 mL ropivacaine 7.5 mg/mL (in = 73) or bupivacaine 2.5 mg/mL (n = 71 ) for postoperative pain relief. Pain at rest, on mobilization, and on coughing was assessed repeatedly during 24 hours using a visual analog scale. The patients' ability to walk and the need for supplementary analgesics were also recorded. RESULTS: No statistically significant differences were found between the two groups with respect to pain scores, which the patients reported to be less than 15% (median) of the worst pain imaginable in all examinations performed at rest, or in the consumption of supplementary analgesics. Those who received ropivacaine could walk with no or only minor problems at an earlier stage than the bupivacaine patients (P < .03). Both treatments were well tolerated. CONCLUSIONS: Wound infiltration with long-acting local anesthetics resulted in low pain scores after hernia surgery. Bupivacaine 100 mg was as effective as ropivacaine 300 mg.

Perception of body odor-an overlooked consequence of long-term gastrointestinal and urinary symptoms after radiation therapy for prostate cancer.

PURPOSE: This study was conducted to investigate the association of long-term gastrointestinal and urinary symptoms with perceived fecal or urine body odor after radiation therapy for prostate cancer and its effect on survivors' quality of life. METHODS: We used a study-specific questionnaire to measure the occurrence of long-term gastrointestinal and urinary symptoms, the perception of fecal or urine body odor, and quality of life (QoL) 2 to 14 years after radiation therapy for prostate cancer. The questionnaire was sent to 895 eligible survivors who assessed symptom occurrence and QoL in the previous 6 months. RESULTS: We received a filled-in questionnaire from 874 (89 %) men. For the long-term gastrointestinal symptoms, 11/13 were associated with the perception of fecal body odor. For the long-term urinary symptoms, 11/11 were associated with the perception of urine body odor. Men who perceived fecal or urine body odor had a lower quality of life, a lower physical health, and more frequent feelings of depression compared with those who did perceive such body odor. CONCLUSION: Long-term gastrointestinal and urinary symptoms after prostate irradiation are associated with the perception of fecal or urine body odor leading to a reduced quality of life. IMPLICATIONS FOR CANCER SURVIVORS: Disabling body odor after pelvic irradiation needs to be acknowledged in the clinic. Interventions to prevent long-term symptoms may serve the benefit of avoiding fecal or urine body odor after radiation therapy for prostate cancer.

Superiority of intensity-modulated radiotherapy over three-dimensional conformal radiotherapy combined with brachytherapy in nasopharyngeal carcinoma: a planning study.

A planning study was performed in order to investigate the potential benefits of intensity-modulated radiotherapy using a simultaneous integrated multi-target treatment technique (SIMT-IMRT) over highly optimized three-dimensional conformal radiotherapy combined with intracavitary brachytherapy (3D-CRT + IBT) for the treatment of nasopharyngeal carcinoma (NPC). The subjects were eight patients with Stages I-IV NPC. For each case, two sets of plans were prepared after delineation of gross tumour volumes, three planning target volumes (PTVs) and 17 organs at risk (OARs). Dose prescriptions for PTVs were 72.6 Gy, 66 Gy and 52.8 Gy in 33 fractions for SIMT-IMRT vs 72 Gy (66 Gy in 33 fractions for 3D-CRT and 3 Gy twice for IBT), 66 Gy (in 33 fractions) and 46 Gy (in 23 fractions) for 3D-CRT + IBT plans. Compared with the combined plans, SIMT-IMRT provided superior results for the primary tumour (PT) in terms of mean equivalent uniform dose (67 Gy vs 63.7 Gy, p = 0.016). IMRT plans increased the mean tumour control probability (TCP) values (both uncorrected and corrected for accelerated tumour repopulation after 28 days) for PT when compared with 3D-CRT + IBT (98% and 94.3% vs 95.8% and 89.9%, respectively, p = 0.016). Mean doses to middle/external ears, parotid glands and temporomandibular joints were significantly lower in IMRT plans. Our conclusion is that, for all stages of NPC, SIMT-IMRT was superior to highly optimized 3D-CRT + IBT in terms of tumour coverage, increased local TCP, and dose reduction to some OARs. We recommend that SIMT-IMRT should be considered as a first-line radiotherapy technique for NPC.

Patients with atherosclerosis may have increased circulating levels of 27-hydroxycholesterol and cholestenoic acid.

Extrahepatic sterol 27-hydroxylase (CYP27) appears to have a role in the elimination of excess cholesterol from various cells, particularly macrophages, and there is a net flux of 27-hydroxyycholesterol and its metabolites from different extrahepatic sources to the liver. In this study we tested the hypothesis that patients with advanced atherosclerosis may have higher levels of 27-oxygenated products in the circulation than control subjects. Concordant with previous studies, a strong correlation was observed between circulating levels of 27-hydroxycholesterol and cholesterol, in both healthy subjects and subjects with hypercholesterolemia and documented atherosclerosis. A group of male subjects with normal or only slightly elevated serum cholesterol and rapidly progressing carotid atherosclerosis (n = 20) had serum levels of 27-oxygenated cholesterol not statistically different from those of a matched group of subjects with little or no development of atherosclerosis (n = 20). The situation was similar in a group of patients (n = 20) with advanced general atherosclerosis associated with severe clinical symptoms. Among the two groups of patients with atherosclerosis, a few patients had relatively high levels of 27-oxygenated products. Among the healthy controls, two healthy volunteers (brother and sister) were found to have high levels of 27-hydroxycholesterol, most probably due to genetic reasons. The possibility is discussed that the high levels of 27-oxygenated products in the circulation of a few patients with atherosclerosis may be related to high amounts of active macrophages present in atherosclerotic lesions. In view of the number of factors that could affect the levels in the circulation, other explanations cannot be ruled out. At the present state of knowledge, measurements of circulating levels of 27-oxygenated metabolites do not seem to add useful information about the atherosclerotic process.

Polyglycolic acid (Dexon) mesh graft for abdominal wound support in healing-compromised patients.

In 25 patients operated on for colorectal carcinoma via a paramedian incision, the anterior fascia of the rectus muscle was strengthened with a polyglycolic acid mesh graft. No adverse effects related to the mesh were detectable in these potentially contaminated patients, and none showed any sign of wound infection or wound herniation. The polyglycolic acid mesh graft thus can be successfully used as a support for abdominal wounds, especially in patients at elevated risk of infection or rupture of the wound.

Efficacy of subcutaneous and topical local anaesthesia for pain relief after resection of malignant breast tumours.

OBJECTIVE: Infiltration and topical application of local anaesthetics close to the surgical wound may be used to prevent postoperative pain. We evaluated the efficacy of these treatments after breast surgery for cancer. DESIGN: Double-blind randomised trial with two treatment groups and one control group. SETTING: University hospital, Sweden. INTERVENTIONS: Patients were allocated to treatment with bupivacaine infiltration (n = 29), topical application of lignocaine/prilocaine (n = 31), or no local treatment (n = 30). MAIN OUTCOME MEASURES: Difference and time related patterns in pain scores measured on a visual analogue scale (VAS), and morphine consumption. RESULTS. None of the local anaesthetics significantly reduced the VAS score or morphine consumption. However, fewer patients in the anaesthetic groups had high VAS scores than controls, the 75 centile for the mean score after operation being 2.7, 2.0 and 2.1 for the controls, infiltration, and topical anaesthetic groups, respectively. The controls had higher scores from 6 hours postoperatively onwards. The corresponding median morphine consumption was 24.5, 18.5, and 16.2 mg. CONCLUSIONS. Local anaesthesia slightly reduced the overall pain scores and the morphine consumption, but was of potential clinical value only in the patients who had the highest pain scores.

Sensory and sympathetic block during interpleural analgesia.

BACKGROUND AND OBJECTIVES: Interpleural analgesia is an effective method for pain relief after upper abdominal surgery. To examine whether the analgesic effect is obtained by block of the intercostal nerves, we assessed the analgesic efficacy of the block, the skin sensitivity, and indices of sympathetic outflow over the trunk. METHODS: Interpleural analgesia was instituted at the end of open cholecystectomy in 20 patients 24-81 years of age (mean, 42 years). After a washout period of 8 hours, the analgesic effect was tested 5-12 times during the postoperative follow-up period by using a visual analogue scale before and 20 minutes after injection of 20 mL of bupivacaine 0.25%. Temperature and pain sensations were tested on the day after surgery, and in nine of the patients, the cutaneous blood flow over the trunk was studied by an electronic thermometer, laser Doppler flowmetry, and fluorescein flowmetry. In addition, the conduction velocity in the phrenic nerve was studied in four of the patients. RESULTS: Interpleural analgesia significantly reduced the median visual analogue score from of 5.7 (range 2-10) to 1.1 (range, 0-4). Although the analgesic effect was very good in all patients, half of them still showed skin sensitivity to pain and temperature. Cutaneous blood flow did not change, which showed than block of the intercostal nerves was incomplete. The phrenic nerve was not affected. CONCLUSION: The incomplete cutaneous sensory and sympathetic block indicates that the analgesic effect of interpleural analgesia cannot be explained by retrograde diffusion of the local anesthetic solution into the intercostal nerves alone.

Balloon catheters. In vitro experiments on pressure influence and risk of rupture.

Balloon catheters with latex balloons were inflated in plastic tubes of different diameters. The volume at rupture of the balloons was measured. The pressure inside the balloon and that caused by the balloon against the tube walls were recorded. Measures to avoid high pressure on the vessel wall, and balloon rupture, are discussed.

Postoperative analgesia with intrapleural administration of bupivacaine-adrenaline.

Twenty-one patients who underwent elective cholecystectomy were studied with regard to the effect of intrapleural administration of bupivacaine-adrenaline solution on postoperative pain and ventilatory capacity. Administration of 10 or 20 ml of 2.5 mg/ml or 5 mg/ml bupivacaine solution resulted in complete analgesia in 143 of 159 administrations. Most patients experienced the maximal pain-relieving effect within 1-2 min and analgesia persisted as a rule for 3-5 h. Forced vital capacity and forced expiratory volume in 1 s increased after intrapleural analgesia on average by 56% and 46%, respectively, on the first postoperative day and by 35% and 51%, respectively, on the second day. There was no significant difference in the analgesic effect or in the effect on the ventilatory capacity between the 2.5 mg/ml or the 5 mg/ml solution, in either the 10 ml or the 20 ml dose. Placebo (NaCl) given intrapleurally had no effect on pain or on the ventilatory capacity. The plasma concentration of bupivacaine after intrapleural administration showed a wide interindividual variation, with considerably higher average values when the 5 mg/ml solution had been used than for the 2.5 mg/ml solution. Although no toxic effects were noted, a 2.5 mg/ml solution, which can be given in an initial dose of 20 ml and top-up doses of 10 ml at 3-6 h intervals, is recommended. In four patients minor pneumothorax developed when the catheter was introduced. The pneumothorax was easily evacuated, but underlines the need for great care when introducing the catheter.

Prospective randomised comparison of adjustable gastric banding and vertical banded gastroplasty for morbid obesity.

OBJECTIVE: To compare the clinical results of adjustable gastric banding and vertical banded gastroplasty for morbid obesity. DESIGN: Prospective randomised trial. SETTING: University hospital, Sweden. PATIENTS: 59 morbidly obese patients, listed for obesity surgery. INTERVENTIONS: Adjustable gastric banding (n = 29) or vertical banded gastroplasty (n = 30). MAIN OUTCOME MEASURES: Weight loss, complications, need for revisional surgery, reflux symptoms and the patient's own evaluation. RESULTS: Five years after surgery the mean (SEM) weight reduction for adjustable gastric banding was 43 (3.0) kg and for vertical banded gastroplasty 35 (4.8) kg. One patient in each group died of unrelated causes during follow-up and 3 and 2 patients, respectively, were lost to follow-up. One patient in the vertical banded group required reoperation for an anastomotic leak on the third postoperative day. A total of 3 patients in the adjustable group required reoperation and 11 in the vertical banded group. CONCLUSIONS: Adjustable gastric banding carries a smaller risk of reoperation than vertical banded gastroplasty and the weight reduction is in the same order of magnitude.