Efficacy of hyperthermic intraperitoneal chemotherapy in colorectal cancer: A phase I and III open label randomized controlled registry-based clinical trial protocol.

Standard treatment for patient with peritoneal metastases from colorectal cancer is cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). In recent years, the efficacy of oxaliplatin-based HIPEC has been challenged. An intensified HIPEC (oxaliplatin+irinotecan) in combination with early postoperative intraperitoneal chemotherapy (EPIC) has shown increased recurrence-free survival in retrospective studies. The aim of this trial is to develop a new HIPEC/EPIC regimen and evaluate its effect on morbidity, oncological outcome, and quality-of-life (QoL). This study is designed as a combined phase I/III multicenter randomized trial (RCT) of patients with peritoneal metastases from colorectal cancer eligible for CRS-HIPEC. An initial phase I dose escalation study, designed as a 3+3 stepwise escalation, will determine the maximum tolerable dose of 5-Fluorouracil (5-FU) as 1-day EPIC, enrolling a total of 15-30 patients in 5 dose levels. In the phase III efficacy study, patients are randomly assigned intraoperatively to either the standard treatment with oxaliplatin HIPEC (control arm) or oxaliplatin/irinotecan-HIPEC in combination with single dose of 1-day 5-FU EPIC (experimental arm). 5-FU is administered intraoperatively after CRS-HIPEC and closure of the abdomen. The primary endpoint is 12-month recurrence-free survival. Secondary endpoints include 5-year overall survival, 5-year recurrence-free survival (registry based), postoperative complications, and QoL up to 3 years after study treatment. This phase I/III trial aims to identify a more effective treatment of colorectal peritoneal metastases by combination of HIPEC and EPIC.

Predicting life with a permanent end colostomy: A prospective study on function, bother and acceptance.

AIM: The factors that influence a patient's experience of a colostomy are not known. The aim of this study was to characterise stoma function, stoma-related bother and acceptance among patients operated for rectal cancer and to investigate if there were any preoperative personal factors with predictive impact on long-term stoma-related bother. METHODS: The QoLiRECT (Quality of Life in RECTal cancer) study is a prospective multicentre study of patients with rectal cancer. This was a subgroup analysis of patients with a permanent colostomy with a 2-year follow-up. Penalised regression models with shrinkage estimation were used to predict the 1-and 2-year bother using baseline data. The predictive value and the importance of the included variables were evaluated using bootstrap resampling techniques. RESULTS: A total of 379 patients were included. Overall stoma acceptance was high and a majority of patients were not bothered by their stoma; 77% and 83% at 1 and 2 years, respectively. The subgroup of patients with stoma-related bother had a high prevalence of difficulties, especially fear of leakage, and a low stoma acceptance in daily life. Both clinical and personal factors were associated with stoma-related bother. The most important factors were quality of life and physical health, but the prediction accuracy was low. CONCLUSIONS: Stoma-related bother was associated with overall stoma dysfunction. As stoma-related bother is a multifactorial problem, it was not possible to predict which patients will experience stoma-related bother. It is therefore of importance to prevent stoma-related symptoms and optimise stoma function to reduce long-term bother and increase stoma acceptance.

Younger age at onset of colorectal cancer is associated with increased patient's delay.

AIM: This study aimed to investigate if younger age at diagnosis of colorectal cancer was associated with a diagnostic delay. The secondary objective was to evaluate if symptomatology varied with age. METHOD: The study population consisted of the cohorts from two prospective multicentre studies conducted in Sweden and Denmark, the QoLiRECT and QoLiCOL studies. These studies investigated the quality of life in patients with colorectal cancer. Participants responded to the validated questionnaires used to extract information on patient's and doctor's delay as well as first presenting symptoms. Clinical variables were retrieved from the Swedish Colorectal Cancer Registry and the Danish Colorectal Cancer Group Database. RESULTS: 2574 patients were included, 1085 from QoLiRECT and 1489 from QoLiCOL. The probability of an increased patient's delay was higher when age decreased by 10 years (the SD in both QoLiRECT and QoLiCOL), adjusted OR 1.19 (95%CI: 1.10; 1.30), p < 0.001. A similar effect was found for doctor's delay, but the age effect was smaller in this case, adjusted OR 1.05 (95%CI: 0.97; 1.15), p = 0.177. When the age effect was analysed non-linearly, an increased probability of a delay was seen for patients from around 60 years and below. Younger patients were equally or more likely to report the symptoms of blood in stool, diarrhoea, constipation, mucus in faeces, faecal urgency, faecal emptying difficulties and pain compared to older patients. CONCLUSION: Younger patients were more likely to have an increased patient's delay, probably contributing to a delayed diagnosis of colorectal cancer. Symptomatology at diagnosis was similar irrespective of age.

Do negative intrusive thoughts at diagnosis predict impaired quality of life, depressed mood and waking up with anxiety 3, 12 and 24 months after radical prostatectomy? - a longitudinal study.

Objective: To evaluate the effect of intrusive thoughts at diagnosis on quality of life, depressed mood and waking up with anxiety up to two years after radical prostatectomy.Method: The Laparoscopic Prostatectomy Robot Open (LAPPRO) trial was a prospective, longitudinal multicenter study of 4003 patients undergoing radical prostatectomy. Questionnaire data were collected preoperatively, at 3, 12 and 24 months after surgery.Results: The group of patients with intrusive thoughts at diagnosis had a statistically significant higher postoperative prevalence of impaired quality of life, depressed mood and waking up with anxiety as compared with the group of patients with no or minor intrusive thoughts. The highest risk increase for impaired QoL, depressed mood and waking up with anxiety ≥1/week was at 12, 3 and 3 months, respectively, where the three outcomes increased by 38% (RR: 1.38; 95%CI: 1.27-1.49)), 136% (RR: 2.36; 95%CI: 1.74-3.19)) and 165% (RR: 2.65; 95%CI: 2.22-3.17)), respectively.Conclusions: The demonstrated link between intrusive thoughts and quality of life, depressed mood and waking up with anxiety deliver is further evidence to the idea that intrusive thoughts has potential as an endpoint for assessing and predicting psychological distress among men with prostate cancer diagnosis.Trial registration number: ISRCTN06393679 (www.isrctn.com). Date of registration: 07/02/2008. Retrospectively registered.

Peritoneal mesothelioma in Sweden: A population-based study.

The study aim was to report survival and morbidity of all patients in Sweden with peritoneal mesothelioma treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as well as investigate whether the survival has increased on a population level since this treatment was nationalized 2011. Study data were collected from the Swedish HIPEC registry and the Swedish National Cancer Registry. All patients with peritoneal mesothelioma scheduled for CRS/HIPEC treatment in Sweden January 2011 to March 2018 were retrieved from the Swedish HIPEC registry. Clinicopathological and survival data were collected. For population-level analysis, all patients with diffuse malignant peritoneal mesothelioma (DMPM) were identified from the Swedish National Cancer Registry and data were retrieved from two separate 5-year time periods: 1999-2003 and 2011-2015. Thirty-two patients were accepted for CRS/HIPEC. Four were open/close cases. Two-year survival rate was 84% or 59% when excluding borderline peritoneal mesotheliomas (n = 17). Median overall survival was not reached. Grade III-IV Clavien-Dindo events occurred in 22% with no mortality. From the national cancer registry, 102 DMPM cases were retrieved: 40 cases between 1999 and 2003, and 62 cases between 2011 and 2015 (corresponding to an increase from 0.9 to 1.24/million/year, P = .04). Six patients (10%) received CRS/HIPEC in the second period. Median OS increased between periods from 7 to 15 months and 5-year survival from 14% to 29% (P = .03). Peritoneal mesothelioma of both borderline and DMPM subtypes undergoing CRS/HIPEC have good long-term survival. The incidence of DMPM in Sweden has increased. Overall survival has increased alongside the introduction of CRS/HIPEC, which may be a contributing factor.

Patients with rectal cancer are satisfied with in-hospital communication despite insufficient information regarding treatment alternatives and potential side-effects.

AIM: Patients with rectal cancer may undergo treatment such as surgery and (chemo)radiotherapy. Before treatment, patients are informed of different options and possible side-effects. The aim of the study was to evaluate the patients' experience of communication with healthcare personnel at time of diagnosis and after one year. METHOD: A total of 1085 patients from Denmark and Sweden were included. They answered a detailed questionnaire at diagnosis and at the one year follow-up. Clinical data were retrieved from national quality registries. RESULTS: Response rates were 87% at baseline and 74% at one year. Overall the patients were very satisfied with the communication with healthcare personnel. However, some patients reported insufficient information regarding treatment options and possible side-effects. Only 32% (335/1050) and 24% (248/1053), respectively, stated that they were informed about possible sexual and urinary dysfunction before treatment. CONCLUSIONS: Even though patients felt that they received insufficient information regarding side-effects on sexual and urinary function, they were generally satisfied with the communication with the healthcare personnel. Since overall satisfaction with the level of information was very high, it is unlikely that further information to patients with rectal cancer in the surgical and oncological settings will improve satisfaction with communication.

Role of matrix metalloproteinases in tumour invasion: immunohistochemistry of peritoneum from peritoneal carcinomatosis.

Colorectal cancer is one of the most common forms of cancer. Spread of tumour to the peritoneal cavity may lead to seeding of cancer cells that adhere to and invade the peritoneal membrane causing peritoneal carcinomatosis. Matrix metalloproteinases (MMPs) play an essential role in cancer cell invasion and dissemination. The aim of this study was to evaluate the morphology and presence of matrix metalloproteinases in peritoneal carcinomatosis. Biopsy samples of the parietal peritoneum were taken from patients undergoing cytoreductive surgery for peritoneal carcinomatosis. The samples were fixed in formalin, dehydrated and embedded in paraffin prior to cutting into 4-µm slices. Staining with haematoxylin/eosin was used for morphology studies, and MMP-1, MMP-2 and TIMP-1 levels were evaluated using immunohistochemistry and light microscopy. The microscopically tumour-free areas of the peritoneal membrane were thin compared to the peripheral invasion zone and the areas invaded by tumour. Peritoneum invaded by tumour was richly vascularised and contained inflammatory cells. MMP-1 was expressed in tumour-free peritoneum and in the invasion zone between tumour and peritoneal tissue, but not in tumour-invaded areas. MMP-2 and TIMP-1 were mostly expressed in the proximity of blood vessels and inflammatory cells in tumour-invaded areas, but was not seen in tumour-free areas. MMPs play an important role in the process of cancer cell invasion of the peritoneum in peritoneal carcinomatosis. The peripheral zone of the tumour appears to be of importance for tumour invasion.

Correction to: Pretreatment quality of life in patients with rectal cancer is associated with intrusive thoughts and sense of coherence.

The original version of this article, unfortunately, contained errors.

Pretreatment quality of life in patients with rectal cancer is associated with intrusive thoughts and sense of coherence.

PURPOSE: Quality of life may predict survival. In addition to clinical variables, it may be influenced by psychological factors, some of which may be accessible for intervention. The primary objective of this study was to investigate the association of intrusive thoughts and the patients' sense of coherence with pretreatment quality of life in patients with newly diagnosed rectal cancer. METHODS: Patients were prospectively included in 16 hospitals in Sweden and Denmark. They answered an extensive questionnaire after receiving their treatment plan. Clinical data were retrieved from national quality registries for rectal cancer. RESULTS: Of 1248 included patients, a total of 1085 were evaluable. Pretreatment global health-related and overall quality of life was lower in patients planned for palliative compared with curative treatment (median 53 vs. 80 on the EuroQoL visual analogue scale, p < 0.001 and odds ratio 0.56, 95% confidence interval 0.36-0.88, respectively). Quality of life was associated with intrusive thoughts (odds ratio 0.33, 95% confidence interval 0.24-0.45) and sense of coherence (odds ratio 0.44, 95% confidence interval 0.37-0.52) irrespective of the treatment plan. CONCLUSIONS: Pretreatment quality of life was influenced by the intent of treatment as well as by intrusive thoughts and the patients' sense of coherence. Interventions could modify these psychological factors, and future studies should focus on initiatives to improve quality of life for this group of patients.

Persistent perineal morbidity is common following abdominoperineal excision for rectal cancer.

PURPOSE: Short-term complications related to the perineal wound after abdominoperineal excision (APE) are a well-known problem. Perineal morbidity in the longer term is an almost unexplored area. The aim of this cross-sectional study was to investigate the prevalence of perineal symptoms 3 years after APE for rectal cancer, to identify potential risk factors and to explore the relationship between perineal morbidity and global quality of life. METHOD: All patients who underwent APE in Sweden between 2007 and 2009 (n = 1373) were identified through the Swedish Colorectal Cancer Registry. Surviving patients were contacted 3 years after surgery and asked about participation. A total of 545 patients completed a detailed questionnaire. Clinical data was collected from the registry and surgical charts. RESULTS: Perineal symptoms occurred in 50 % of all patients 3 years after APE and more frequently in women (58 vs. 44 %; p = 0.001). Delayed healing of the perineal wound (>4 weeks) occurred in 25 % of all patients and more frequently after extralevator APE (ELAPE) than after conventional APE (32 vs. 11 %, p < 0.001). Delayed healing was associated with an increased risk of more severe perineal symptoms (relative risk (RR) 1.50, 95 % confidence interval (95 % CI) 1.09-2.05). Patients with more severe perineal symptoms (n = 129) had a significantly lower global quality of life as measured by EQ-5D visual analogue scale (VAS; median 75 vs. 83 points on the 100-point scale; p < 0.001). CONCLUSION: Persistent perineal symptoms are common after APE and may have an impact on patients' quality of life. Delayed wound healing may be a risk factor for persistent symptoms. Further studies are needed to identify avoidable clinical factors for the development of persistent perineal morbidity. CLINICALTRIALS. GOV IDENTIFIER: NCT01296984.

Self reported experience of sexual function and quality after abdominoperineal excision in a prospective cohort.

INTRODUCTION: Rectal cancer treatment, especially abdominoperineal excision (APE), can cause sexual dysfunction. There are indications that pre-operative information regarding sexual dysfunction is inadequate. The aim of this study was to explore self reported sexual function in a group of patients operated with APE and the patients' remembrance of preoperative information more than one year after their surgical procedure. METHODS: Consecutive patients with rectal cancer operated with APE in one institution between 2004 and 2009 were included. Data was collected from hospital records and the Swedish Colorectal cancer registry. A detailed questionnaire was sent out to the patients 13-84 months post-operatively. RESULTS: One hundred and eight patients were alive in February 2011, 84 agreed to participate and 89% returned the questionnaire. Men and women did not differ regarding age, tumour stage, neoadjuvant treatment or type of surgical procedure. More men were involved in a relationship; men had more thoughts about sex, were less satisfied and were more bothered than women by their sexual dysfunction. A majority of patients did not retain sufficient knowledge from the preoperative information regarding sexual dysfunction. DISCUSSION: This exploratory study shows that although sexual activity was similar between the two genders, men reported more bother by their self-reported sexual dysfunction after an APE than women did. However, both men and women felt that the preoperative information was inadequate. CONCLUSION: Surgeons should focus more on information about the risk of sexual dysfunction as well as on its treatment at follow-up. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01323166.

Self-reported quality of life and functional outcome in patients with rectal cancer--QoLiRECT.

INTRODUCTION: The treatment of rectal cancer has improved, and survival rates today exceed those of colon cancer, but functional impairments and other adverse effects of treatment are common among patients. The impact of treatment on patients' quality of life (QoL) remains unclear. Many of the common QoL instruments are brief and not sufficiently detailed to provide a deeper understanding of the factors that determine QoL. The aim of this study was to explore patients' experiences and long-term QoL in an unselected cohort of patients with rectal cancer. METHODS: This is a prospective international multicentre study based on a comprehensive, validated questionnaire on functional impairments and QoL administered to an unselected population of 1,500 patients with rectal cancer at diagnosis and after one, two and five years. The clinical characteristics are retrieved from the national quality registers. A total of 14 hospitals in Sweden and Denmark are currently involved in the study. Inclusion is ongoing, and new including hospitals are welcome to join. Full accrual is expected within two years. CONCLUSION: This study will provide detailed knowledge about the challenges that patients face following diagnosis and treatment of rectal cancer. It will investigate the nature, severity and perceived significance of constraints and symptoms, as well as the impact of a variety of clinical and patient-related factors on QoL. The study will probably identify areas where changes in care routines may improve patients' QoL. FUNDING: This study was supported by the Swedish Research Council, grant number 2012-1768; the Swedish Cancer Society CAN 2010/593 and CAN 2013/500; the Swedish Society of Medicine; the Gothenburg Medical Society; the Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland; ALF grant 138751 and 136151, "Agreement concerning research and education of doctors"; Anna-Lisa and Bror Björnsson Foundation; Assar Gabrielsson Foundation; Mary von Sydow Foundation; Ruth and Richard Julin's Foundation and Lion's Cancer Research Foundation of Western Sweden. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01477229).

Stenting for colorectal cancer obstruction compared to surgery--a study of consecutive patients in a single institution.

BACKGROUND: Colonic obstruction is a common complication to colorectal cancer and surgical treatment is associated with high morbidity and mortality. Stenting has emerged as an alternative to surgery. The aim of this study was to compare short-term morbidity, mortality and hospital stay between treatment with self-expandable metallic stent and emergency surgery performed at our department during a 5-year period in a non-randomized setting. METHODS: Patients with colonic obstruction due to rectal or colon cancer referred to the Endoscopic Unit or Surgical Department for insertion of a colonic stent between 1 August 2003 and 1 August 2008 were prospectively registered and followed (n = 112). A control group was identified using the hospital records of operations with the International Classification Code-10 (ICD-10) for bowel obstruction and colorectal cancer (n = 60). Age, gender, indication, preoperative investigations, surgical procedure, complications and procedure-related mortality were registered. Patients were followed in accordance with local guidelines. RESULTS: The complication rate was similar in the two groups, although there was a trend toward a higher number of severe complications in the surgical group. The hospital stay was significantly lower in the stent group, median of 4 vs. 9 days (p < 0.0001). The procedure-related mortality was lower in the stent group; 7% vs. 20% (p < 0.05). CONCLUSIONS: Stenting can be safely performed with lower or similar complication rate and lower mortality rate compared to surgery and results in significantly shorter hospital stay. The results support stenting as the treatment of choice in patients with acute colonic obstruction, especially in disseminated disease.