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  • 1.
    Iselius, Sofia
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Knutsen, Annica
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Mikiver, Rasmus
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regionledningskontoret, Regional Cancer Center.
    Uppugunduri, Srinivas
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regionledningskontoret, Regional Cancer Center.
    Late adverse events in patients with pelvic cancer after oncologic treatment-intervention and treatment effect2023In: Supportive Care in Cancer, ISSN 0941-4355, E-ISSN 1433-7339, Vol. 31, no 5, article id 263Article in journal (Refereed)
    Abstract [en]

    PurposeFew studies have focused on the late adverse events after oncologic treatment in pelvic cancer patients. Here, the treatment effect/interventions were studied on late side effects as GI, sexual, and urinary symptoms in pelvic cancer patients who visited a highly specialized rehabilitation clinic in Linkoping.MethodsThis retrospective longitudinal cohort study included 90 patients who had at least one visit at the rehabilitation clinic for late adverse events at Linkoping University hospital between 2013 to 2019. The toxicity of the adverse events was analyzed by using the common terminology criteria for adverse events (CTCAE).ResultsBy comparing the toxicity of symptoms between visits 1 and 2, we showed that the GI symptoms decreased with 36.6% (P = 0.013), the sexual symptoms with 18.3% (P < 0.0001), and urinary symptoms with 15.5% (P = 0.004). Patients who received bile salt sequestrant had a significant improvement in grade of GI symptoms as diarrhea/fecal incontinence at visit 2 compared to visit 1 where 91.3% were shown to have a treatment effect (P = 0.0034). The sexual symptoms (vaginal dryness/pain) significantly improved due to local estrogens between visits 1 and 2 where 58.1% had a reduction of symptoms (P = 0.0026).ConclusionThe late side effects as GI, sexual, and urinary symptoms was significantly reduced between visits 1 and 2 at the specialized rehabilitation center in Linkoping. Bile salt sequestrants and local estrogens are effective treatments for side effects as diarrhea and vaginal dryness/pain.

  • 2.
    Vernmark, Karolina
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Knutsen, Annica
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Loftås, Per
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Sun, Xiao-Feng
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    The impact of adjuvant chemotherapy on survival in mucinous and non-mucinous rectal adenocarcinoma patients after TME surgery2023In: PLOS ONE, E-ISSN 1932-6203, Vol. 18, no 2Article in journal (Refereed)
    Abstract [en]

    IntroductionThe value of adjuvant chemotherapy for rectal cancer patients is debated and varies in different subgroups. One such subgroup is mucinous adenocarcinoma (MAC), which is more treatment resistant compared to non-mucinous adenocarcinoma (NMAC). To date, mucinous histology is not taken into account when deciding on adjuvant treatment strategy. This is the first study to exclusively include patients with rectal cancer, then separate MAC and NMAC and compare the survival in patients that had or did not have adjuvant chemotherapy. Material and methodsThe study included retrospective register data from 365 Swedish patients with stage II-IV rectal adenocarcinoma, 56 patients with MAC and 309 patients with NMAC. All patients were considered curative, had surgery with total mesorectal excision in 2004-2013, and were followed up until death or 2021. ResultsPatients with MAC that had adjuvant chemotherapy had better overall survival (OS, HR 0.42; CI 95%: 0.19-0.93; p = 0.032) and a trend towards better cancer-specific survival (CSS, HR 0.41 CI 95%: 0.17-1.03; p = 0.057) compared to patients without chemotherapy (HR 0.42; CI 95%: 0.19-0.93; p = 0.032). The difference in OS was still significant even after adjusting for sex, age, stage, differentiation, neoadjuvant chemotherapy and preoperative radiotherapy (HR 0.40; CI 95%: 0.17-0.92; p = 0.031). There was no such difference in the NMAC patients except in the stage-by-stage subgroup analyses where patients in stage IV had better survival after adjuvant chemotherapy. ConclusionsThere may be a difference in treatment response to adjuvant chemotherapy between MAC and NMAC patients. Patients with MAC could possibly benefit from adjuvant chemotherapy in stages II-IV. Further studies are however needed to confirm these results.

  • 3.
    Holmqvist, Annica
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Lindahl, Gabriel
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology.
    Mikivier, Rasmus
    Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regionledningskontoret, Regional Cancer Center.
    Uppugunduri, Srinivas
    Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regionledningskontoret, Regional Cancer Center.
    Age as a potential predictor of acute side effects during chemoradiotherapy in primary cervical cancer patients2022In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 22, no 1, article id 371Article in journal (Refereed)
    Abstract [en]

    Background

    Toxicity during chemoradiotherapy (CRT) in cervical cancer patients might limit the chances of receiving an optimal treatment and to be cured. Few studies have shown relationships between acute side effects and patients age. Here, the association between age and acute side effects such as nausea/vomiting, diarrhea and weight loss during CRT was analysed in cervical cancer patients.

    Methods

    This study included 93 patients with primary cervical cancer stage IBI to IVA who received CRT from 2013 to 2019. The frequency of symptoms/toxicity grade was analysed by using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

    Results

    Patients ≥ 52 years had a significantly higher frequency of nausea/vomiting and increased grade  ≥ 3 toxicity during CRT compared to younger patients (p<0.001, p = 0.001). Toxicity grade ≥ 3 of nausea/vomiting was associated with increased frequency of weight loss (p = 0.001), reduced ADL (p = 0.001) and dose modifications of both radiotherapy (RT) (p = 0.020) and chemotherapy (CT) (p = 0.030) compared to toxicity grade 2. The frequency of diarrhea (p = 0.015) and weight loss (p = 0.020) was higher in older patients compared to younger.

    Conclusions

    Older patients have an increased risk of acute side effects as nausea/vomiting, diarrhea and weight loss. Age could be useful in predicting acute side effects in primary cervical cancer patients with CRT.

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  • 4.
    Holmqvist, Annica
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Axelsson, A.
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Mikiver, Rasmus
    Region Östergötland, Regionledningskontoret, Regional Cancer Center.
    Redelius, K.
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Odelram Wireen, U.
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regionledningskontoret, Regional Cancer Center.
    Uppugunduri, Srinivas
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regionledningskontoret, Regional Cancer Center.
    Urologic, lymphedema, pelvic pain and gastrointestinal symptoms increase after radiotherapy in patients with primary uterine tumors: a prospective longitudinal Swedish cohort study2021In: Clinical and Translational Oncology, ISSN 1699-048X, E-ISSN 1699-3055, Vol. 23, no 9, p. 1752-1760Article in journal (Refereed)
    Abstract [en]

    Purpose Radiotherapy (RT) causes an inflammatory reaction of the tissue which leads to fibrosis and reduced functioning of the pelvic organs. Few studies have shown significant relationships between side effects and RT in uterine tumors. Here, the urological, lymphedema, pelvic pain and gastrointestinal (GI) symptoms were studied before and after RT in patients with primary uterine tumors using the EORTC QLQ-EN24, specifically designed for uterine cancer patients. Methods This prospective cohort study comprised patients with primary uterine tumors who received pelvic radiotherapy (RT). A total of 43 patients were included from May 2014 to February 2019. Patients completed the questionnaires for global health status and functioning before the start of RT and at 3 and 12 months after RT. Results We found a significant worsening of the urological symptoms 3 months after RT which persisted up to 12 months after RT compared to baseline values prior to start of RT (p = 0.007). An exacerbation of the urinary symptoms was seen in patients with vaginal brachytherapy/boost compared to patients with pelvic RT at 12 months after RT (p = 0.053). The severity of lymphedema symptoms increased from RT start to 12 months after RT (p = 0.019) and the pelvic pain were higher at 3 months after RT compared to before RT (p = 0.004). Also, the level of GI symptoms was significantly higher 12 months after RT compared to the RT start (p &lt; 0.001). Conclusions The urologic, lymphedema, pelvic pain and GI symptoms all increase after RT.

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  • 5.
    Vernmark, Karolina
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Sun, Xiao-Feng
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Holmqvist, Annica
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Mucinous and Non-Mucinous Rectal Adenocarcinoma - Differences in Treatment Response to Preoperative Radiotherapy2020In: Journal of Personalized Medicine, E-ISSN 2075-4426, Vol. 10, no 4, article id 226Article in journal (Refereed)
    Abstract [en]

    There is a need to personalize the treatment for rectal cancer patients. The aim of this study was to analyze therapy response and prognosis after preoperative radiotherapy in rectal cancer patients with mucinous adenocarcinoma compared to those with non-mucinous adenocarcinoma. The study included retrospectively collected data from 433 patients, diagnosed with rectal cancer in the South East health care region in Sweden between 2004 and 2012. Patients with non-mucinous adenocarcinoma that received short-course radiotherapy before surgery had better overall survival, cancer specific survival, and disease-free survival, as well as distant- and local-recurrence-free survival (p = 0.003, p = 0.001, p = 0.002, p = 0.002, and p = 0.033, respectively) compared to the patients that received long-course radiotherapy with concomitant capecitabine. The results were still significant after adjusting for sex, age, stage, differentiation, and chemotherapy in the neoadjuvant and/or adjuvant setting, except for local-recurrence-free survival that was trending towards significance (p = 0.070). In patients with mucinous adenocarcinoma, no difference in survival was seen when comparing patients that had short-course radiotherapy and patients that had long-course radiotherapy. However, none of 18 patients with mucinous adenocarcinoma treated with long-course radiotherapy had local tumor progression, compared to 7% of 67 patients with non-mucinous adenocarcinoma. The results indicate that mucinous adenocarcinoma and non-mucinous adenocarcinoma may respond differently to radiotherapy.

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  • 6.
    Wen, Yugang
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Shanghai Jiao Tong Univ, Peoples R China.
    Zhao, Senlin
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Shanghai Jiao Tong Univ, Peoples R China.
    Holmqvist, Annica
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Hahn-Stromberg, Victoria
    Uppsala Univ, Sweden.
    Adell, Gunnar
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Holmlund, Birgitta
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Pathak, Surajit
    Chettinad Acad Res & Educ, India.
    Peng, Zhihai
    Shanghai Jiao Tong Univ, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Predictive Role of Biopsy Based Biomarkers for Radiotherapy Treatment in Rectal Cancer2020In: Journal of Personalized Medicine, E-ISSN 2075-4426, Vol. 10, no 4, article id 168Article in journal (Refereed)
    Abstract [en]

    Background and Purpose: Radiation therapy has long been contemplated as an important mode in the treatment of rectal cancer. However, there are few ideal tools available for clinicians to make a radiotherapy decision at the time of diagnosis for rectal cancer. The purpose of this study was to assess whether biomarkers expressed in the biopsy could help to choose the suitable therapy and provide predictive and/or prognostic information. Experimental Design: In total, 30 biomarkers were analyzed in 219 biopsy samples before treatment to discover the possibility of using them as an indicator for radiotherapy selection, diagnosis, survival and recurrence. Results: Twenty-two biomarkers (COX2-RT, COX2-NonRT, etc.; 36.67%) had diagnostic value. For survival, four biomarkers (NFKBP65, p130, PINCH and PPAR) were significant in regulating gene promoter activity and overall survival, while four had a trend (AEG1, LOX, SATB1 and SIRT6). Three biomarkers (COX2, PINCH and WRAP53) correlated with disease-free survival, while eight had a trend (AEG1, COX2, Ki67, LOX, NFKBP65, PPAR and SATB1). Four biomarkers (COX2-RT, NFKBP65cyto-RT, P130cyto-NonRT and PPARcyto-RT) were independent prognostic factors for recurrence. NFKBP65 and SIRT6 were significantly correlated with lymph node metastasis regardless of radiation. Patients with high AEG1, LOX, NFKBP65, PPAR and SATB1 had or showed a positive trend for better survival after radiotherapy, while those with positive PINCH and WRAP53 expression would not benefit from radiotherapy. Conclusions: AEG1, LOX, NFKBP65cyto, PPAR and SATB1 could be used as indicators for choosing radiotherapy. COX2-RT, COX2-NonRT and some other biomarkers may provide additional help for diagnosis.

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  • 7.
    Kotti, Angeliki
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Department of Medical and Health Sciences.
    Holmqvist, Annica
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Albertsson, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Survival benefit of statins in older patients with rectal cancer: A Swedish population-based cohort study2019In: Journal of Geriatric Oncology, ISSN 1879-4068, E-ISSN 1879-4076, Vol. 10, no 5, p. 690-697Article in journal (Refereed)
    Abstract [en]

    Objectives

    Increasing evidence suggests that statins may have antitumor effects but their rolein rectal cancer appears inconclusive. The aim of this study was to investigate whether statins may have an impact on survival of older and younger patients with rectal cancer.

    Materials and Methods

    This study included 238 patients ≥70 years and 227 patients <70 years old, from the Southeast Health Care Region of Sweden, who were diagnosed with rectal adenocarcinoma between 2004 and 2013.

    Results

    In the older group (n = 238), statin use at the time of diagnosis was related to better cancer-specific survival (CSS) and overall survival (OS), compared to non-use (CSS: Hazard Ratio (HR), 0.37; 95% CI, 0.19–0.72; P = .003; OS: HR, 0.62; 95% CI, 0.39–0.96; P = .032). In the older group with stages I-III disease (n = 199), statin use was associated with better disease-free survival (DFS) compared to non use (HR, 0.18; 95% CI, 0.06–0.59; P = .005). The improvement of CSS, OS and DFS remained significant after adjusting for potential confounders. In the older group with stage III disease, statin users had better CSS and DFS compared to non-users (log rank P = .043; log-rank P = .028, respectively). In the older group with short course radiotherapy, statin use was related to better CSS (log-rank P = .032). No such association was present in the younger group.

    Conclusion

    Statin use was related to improved survival in older patients with rectal cancer.

    This observation is important given the low cost and safety of statins as a drug.

  • 8.
    Andersson, Ellen
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Albertsson, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Holmqvist, Annica
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    GRACE: Geriatric patients tReated with Avastin in CRC multiple linEs2017In: Clinical Practice, ISSN 2044-9038, E-ISSN 2044-9046, Vol. 14, no 3, p. 175-182Article in journal (Refereed)
    Abstract [en]

    Continuous treatment with bevacizumab in elderly patients with mCRC: A phase IV prospective, open-label, single-arm trial to evaluate outcomes and safety with continuous bevacizumab treatment in combination with chemotherapy over disease progression.

  • 9.
    Vernmark, Karolina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Albertsson, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Björnsson, Bergthor
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Gasslander, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland. Linköping University, Faculty of Medicine and Health Sciences.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Holmqvist, Annica
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    From palliative to curative treatment - stage IV mucinous adenocarcinoma, successfully treated with metronomic capecitabine in combination with Bevacizumab and surgery- a case report2015In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 15, no 884Article in journal (Refereed)
    Abstract [en]

    Background: Mucinous adenocarcinoma (MAC) represents 6-19 % of all colorectal carcinoma. It is associated with poorer response to chemotherapy and chemoradiotherapy. Case presentation: A 27-year-old Swedish woman presented with stomach pain and weight loss, and was diagnosed with locally advanced MAC in the transverse colon as well as 3 liver metastases. Neoadjuvant treatment with fluorouracil, folinic acid and oxaliplatin (FLOX) failed due to several infections, pulmonary embolism and deteriorated performance status. The patient was therefore considered palliative. Palliative treatment with metronomic capecitabine 500 mg x 2 daily and bevacizumab every other week were initiated. After 4 months of treatment the tumors had regressed and the patient was able to undergo radical surgery, thereby changing the treatment intention from palliative to curative. No adjuvant chemotherapy was given. There were no signs of recurrence 9 months later. Conclusions: The role of the combination of metronomic capecitabine and bevacizumab in patients with MAC merits further investigation.

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  • 10.
    Wang, Mo-Jin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Ping, Jie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Li, Yuan
    Sichuan University, Peoples R China.
    Holmqvist, Annica
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Adell, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Zhang, Hong
    University of Örebro, Sweden.
    Zhou, Zong-Guang
    Sichuan University, Peoples R China; .
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Sichuan University, Peoples R China.
    Prognostic Significance and Molecular Features of Colorectal Mucinous Adenocarcinomas: A Strobe-Compliant Study2015In: Medicine, ISSN 0025-7974, E-ISSN 1536-5964, Vol. 94, no 51, p. e2350-Article in journal (Refereed)
    Abstract [en]

    Mucinous adenocarcinoma (MC) is a special histology subtype of colorectal adenocarcinoma. The survival of MC is controversial and the prognostic biomarkers of MC remain unclear. To analyze prognostic significance and molecular features of colorectal MC. This study included 755,682 and 1001 colorectal cancer (CRC) patients from Surveillance, Epidemiology, and End Results program (SEER, 1973 2011), and Linkoping Cancer (LC, 1972-2009) databases. We investigated independently the clinicopathological characteristics, survival, and variety of molecular features from these 2 databases. MC was found in 9.3% and 9.8% patients in SEER and LC, respectively. MC was more frequently localized in the right colon compared with nonmucinous adenocarcinoma (NMC) in both SEER (57.7% vs 37.2%, P &lt; 0.001) and LC (46.9% vs 27.7%, P &lt; 0.001). Colorectal MC patients had significantly worse cancer-specific survival (CSS) than NMC patients (SEER, P &lt; 0.001; LC, P = 0.026), prominently in stage III (SEER, P &lt; 0.001; P=0.023). The multivariate survival analysis showed that MC was independently related to poor prognosis in rectal cancer patients (SEER, hazard ratios [HR], 1.076; 95% confidence intervals [CI], 1.057-1.096; P &lt; 0.001). In LC, the integrated analysis of genetic and epigenetic features showed that that strong expression of PINCH (HR, 3.954; 95% CI, 1.493-10.47; P = 0.013) and weak expression of RAD50 (HR 0.348, 95% CT, 0.106-1.192; P=0.026) were significantly associated with poor CSS of colorectal MC patients. In conclusion, the colorectal MC patients had significantly worse CSS than NMC patients, prominently in stage III. MC was an independent prognostic factor associated with worse survival in rectal cancer patients. The PINCH and RAD50 were prognostic biomarkers for colorectal MC patients.

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  • 11.
    Jung, Michaela
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Holmqvist, Annica
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Albertsson, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    A clinical study of metastasized rectal cancer treatment: assessing a multimodal approach2014In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 31, no 3, p. 839-Article in journal (Refereed)
    Abstract [en]

    Metastasized rectal cancer has long been considered incurable. During recent years, the treatment of rectal cancer patients has been improved, and nowadays, a subgroup of patients might even be cured. The aim of this study was to investigate the optimal timing of treatment in a multimodal therapy schedule in order to see whether the addition of bevacizumab (Avastin) to conventional chemotherapy was effective. The study included 39 patients with metastatic rectal cancer between 2009 and 2011, and three were excluded due to the lack of metastases or lack of follow-up information. The remaining 36 patients were divided into groups by treatment intention. The group with curative intention received mainly oxaliplatin (Eloxatin) in combination with capecitabine (Xeloda) with or without bevacizumab (Avastin) for 2 months followed by preoperative radiotherapy (RT) and surgery. Palliative patients had very different treatments depending on their needs of palliation. The median survival time for patients with curative intention was 31 months and for the palliative patients 12 months. Four of the patients (11%) with curative intention were considered cured at the end of follow-up. The response to chemotherapy after 2-month treatment is a good prognostic sign for which patients can be cured. Long-lasting palliation can be obtained with this treatment schedule. The main side effects were gastrointestinal events, including bowel perforation, neuropathy, thrombo-embolic disease and reduced general condition. All side effects are known, and the treatment is considered tolerable. We conclude that a good treatment schedule would be oxaliplatin (Eloxatin) in combination with capecitabine (Xeloda) with or without bevacizumab (Avastin) for 2 months, followed by preoperative RT and surgery.

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  • 12.
    Miger, Jasmine
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Holmqvist, Annica
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Albertsson, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Low-dose capecitabine (Xeloda) for treatment for gastrointestinal cancer2014In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 31, no 3, p. 870-Article in journal (Refereed)
    Abstract [en]

    The prodrug capecitabine (Xeloda) has been an important drug for treatment for gastrointestinal cancer (GI-cancer). This study explores the efficacy of continuous metronomic Xeloda, as well as tolerability and best response during treatment. Patients (n=35) with stage IV GI-cancer were included in the study and were divided into two groups; upper (n=13) and lower (n=22) GI-cancer. All patients were given continuous metronomic Xeloda (500 mg×2). Best response was measured by radiological and clinical examination including laboratory results. Standard RECIST criteria were used. Median age was 66 (range 29-86). Those patients who received first and second line had the longest duration of treatment. For patients with metastatic gastrointestinal cancer, metronomic capecitabine (Xeloda) may be beneficial both as far as tumor control and quality of life is concerned. In this pilot study, palliation for more than 2 years is observed for 6 of the 35 patients.

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  • 13.
    Kotti, Angeliki
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Holmqvist (Knutsen), Annica
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Albertsson, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    SPARCL1 Expression Increases With Preoperative Radiation Therapy and Predicts Better Survival in Rectal Cancer Patients2014In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 88, no 5, p. 1196-1202Article in journal (Refereed)
    Abstract [en]

    Purpose

    The secreted protein acidic and rich in cysteine-like 1 (SPARCL1) is expressed in various normal tissues and many types of cancers. The function of SPARCL1 and its relationship to a patient's prognosis have been studied, whereas its relationship to radiation therapy (RT) is not known. Our aim was to investigate the expression of SPARCL1 in rectal cancer patients who participated in a clinical trial of preoperative RT.

    Methods and Materials

    The study included 136 rectal cancer patients who were randomized to undergo preoperative RT and surgery (n=63) or surgery alone (n=73). The expression levels of SPARCL1 in normal mucosa (n=29), primary tumor (n=136), and lymph node metastasis (n=35) were determined by immunohistochemistry.

    Results

    Tumors with RT had stronger SPARCL1 expression than tumors without RT (P=.003). In the RT group, strong SPARCL1 expression was related to better survival than weak expression in patients with stage III tumors, independent of sex, age, differentiation, and margin status (P=.022; RR = 18.128; 95% confidence interval, 1.512-217.413). No such relationship was found in the non-RT group (P=.224). Further analysis of interactions among SPARCL1 expression, RT, and survival showed statistical significance (P=.024). In patients with metastases who received RT, strong SPARCL1 expression was related to better survival compared to weak expression (P=.041) but not in the non-RT group (P=.569).

    Conclusions

    SPARCL1 expression increases with RT and is related to better prognosis in rectal cancer patients with RT but not in patients without RT. This result may help us to select the patients best suited for preoperative RT.

  • 14.
    Holmqvist (Knutsen), Annica
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Holmlund, Birgitta
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Ardsby, Malin
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Pathak, Surajit
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    PINCH expression in relation to radiation response in co-cultured colon cancer cells and in rectal cancer patients2013In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 30, no 5, p. 2097-2104Article in journal (Refereed)
    Abstract [en]

    Particularly interesting new cysteine-histidine rich protein (PINCH), involved in cell spreading, motility and proliferation, has been shown to enhance radioresistance in colon cancer cell lines. The expression of PINCH in relation to radiation was studied in co-cultured colon cancer cells. Furthermore, the clinical significance between PINCH and radiotherapy (RT) was analyzed in rectal cancer patients with or without RT. The relative PINCH expression in colon cancer (KM12C) cells cultured separately and in co-culture was examined by western blotting and real-time PCR, and was analyzed over a period of 8 and 24 h after radiation. PINCH expression was immunohistochemically examined in 137 primary rectal tumors for which 65 cases did not receive RT and 72 cases received RT. PINCH expression tended to decrease from that in the separately cultured KM12C cells without radiation to that in cells with radiation at 8 h (P=0.060); while in the co-cultured cells, no significant difference was found (P=0.446). In patients with RT, strong PINCH expression was related to worse survival, when compared to patients with weak expression, independent of TNM stage, degree of differentiation, age and p53 status (P=0.029, RR 4.03, 95% CI 1.34-12.1). No survival relationship for the patients without RT was observed (P=0.287). A statistical interaction analysis between PINCH, RT and survival showed a trend towards significance (P=0.057). In conclusion, PINCH predicts survival in rectal cancer patients with RT, but not in patients without RT. The expression of PINCH may be regulated by radiation and by environmental factors surrounding the cells.

  • 15.
    Holmqvist Knutsen, Annica
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    Gao, Jing-Fang
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Holmlund, Birgitta
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    Adell, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    Carstensen, John
    Linköping University, Department of Medical and Health Sciences, Health and Society. Linköping University, Faculty of Arts and Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    PINCH is an independent prognostic factor in rectal cancer patients without preoperative radiotherapy: A study in a Swedish rectal cancer trial of preoperative radiotherapy2012In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 12, no 65Article in journal (Refereed)
    Abstract [en]

    Background and Purpose: The clinical significance between particularly interesting new cysteine-histidine rich protein (PINCH) expression and radiotherapy (RT) in tumours is not known. In this study, the expression of PINCH and its relationship to RT, clinical, pathological and biological factors were studied in rectal cancer patients.

    Material and Methods: PINCH expression determined by immunohistochemistry was analysed at the invasive margin and inner tumour area in 137 primary rectal adenocarcinomas (72 cases without RT and 65 cases with RT). PINCH expression in colon fibroblast cell line (CCD-18 Co) was determined by Western blot.

    Results: In patients without RT, strong PINCH expression at the invasive margin of primary tumours was related to worse survival, compared to patients with weak expression, independent of TNM stage and differentiation (p = 0.03). No survival relationship in patients with RT was observed (p = 0.64). Comparing the non-RT with RT subgroup, there was no difference in PINCH expression in primary tumours (invasive margin (p = 0.68)/inner tumour area (p = 0.49).

    Conclusions: PINCH expression at the invasive margin was an independent prognostic factor in patients without RT. RT does not seem to directly affect the PINCH expression.

     

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  • 16.
    Holmqvist, Annica E
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    THE LOCATION OF LYMPHANGIOGENESIS IS AN INDEPENDENT PROGNOSTIC FACTOR IN RECTAL CANCERS WITH OR WITHOUT PREOPERATIVE RADIOTHERAPY in ANNALS OF ONCOLOGY, vol 21, issue , pp 212-2122010In: ANNALS OF ONCOLOGY, Oxford University Press , 2010, Vol. 21, p. 212-212Conference paper (Refereed)
    Abstract [en]

    n/a

  • 17.
    Gao, Jingfang
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Knutsen Holmqvist, Annica
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Carstensen, John
    Linköping University, Department of Medicine and Health Sciences, Health and Society. Linköping University, Faculty of Arts and Sciences.
    Franlund, B
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Clinical and biological significance of angiogenesis and lymphangiogenesis in colorectal cancer2009In: DIGESTIVE AND LIVER DISEASE, ISSN 1590-8658, Vol. 41, no 2, p. 116-122Article in journal (Refereed)
    Abstract [en]

    Purpose. The aim of this study was to get a deeper understanding into how adults with cerebral palsy (CP) experience physiotherapy and physical activity in a perspective from childhood to adulthood; and how personal and environmental factors influence possibilities for physiotherapy and physical activity. Method. Data was collected through interviews with 22 community-living adults (35-68 years) with CP, from five counties in Sweden. The questions were open-ended and the interviews were taped and transcribed to written language. The material was analysed through qualitative content analysis, a classification process resulting in different themes. Results. The narratives from the 22 informants, based on experiences from childhood to adulthood, resulted in a description of prerequisites for carrying out physiotherapy and physical activity. Five different themes were identified: (i) Being enjoyable, (ii) Giving effects, (iii) Being comprehensible, (iv) Being integrated in daily life, and (v) Supportive healthcare with competent professionals. Conclusion. The information from the interviews elucidates the importance of a lifelong support from healthcare professionals. Physiotherapists with attentiveness to different life situations in combination with good understanding and knowledge in CP could facilitate continuous physical activity in people growing up and ageing with CP.

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  • 18.
    Bourghardt Peebo, Beatrice
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL.
    Gan, Lisha
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology.
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Knutsen Holmqvist, Annica
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Rearden, Ann
    Fagerholm, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL.
    Expression of the focal adhesion protein PINCH in normal and alkali-injured corneas and the role of PMNs2007In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 85, no 4, p. 395-400Article in journal (Refereed)
    Abstract [en]

    Purpose: To evaluate the role of particularly interesting new cysteine-histidine-rich protein (PINCH) in corneal wound healing and early neovascularization and to assess the influence of granulocytes. Methods: A standardized corneal alkali wound was inflicted under general anaesthesia to the right eye of 14 New Zealand White rabbits. Seven of the rabbits received i.v. 5 mg/kg fucoidin every 2 hours to prevent granulocytes from entering the wound area. After 36 hours, the rabbits were killed, the corneas excised, fixed in 4% formaldehyde and embedded in paraffin. The sections were double-stained with antibodies against PINCH and with haematoxylin. Results: In the normal cornea and limbus, PINCH was weakly expressed in the corneal epithelium and in a wedge of the conjunctival stroma. In the wounded corneas, PINCH expression was seen in the frontline of repopulating endothelial and epithelial cells, and in active keratocytes. The vascular endothelium and the granulocytes expressed PINCH, as did the conjunctival epithelium. In the fucoidin-treated rabbits, PINCH expression was markedly reduced. The vascular endothelial cells and the few granulocytes did not express PINCH in these rabbits. Conclusions: PINCH is only slightly expressed in the normal cornea. A corneal wound induces PINCH expression in the repopulating cells, in the vascular endothelial cells of the limbus, in the limbal epithelium and in the granulocytes. Exclusion of granulocytes reduces expression of PINCH and there is no expression at all in the vascular endothelium. © 2007 The Authors Journal compilation 2007 Acta Ophthalmol Scand.

  • 19.
    Knutsen Holmqvist, Annica
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Adell, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Inflammatory infiltration, fibrosis, necrosis and mucinous content in relation to clinicopathological and molecular factors in rectal cancers with or without preoperative radiotherapy.2006In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 16, no 2, p. 321-327Article in journal (Refereed)
    Abstract [en]

    The association between inflammatory infiltration, fibrosis, necrosis and mucinous content in rectal cancers, and their relationship to preoperative radiotherapy (RT) clinicopathological and biological factors (p53, apoptosis and Cox-2) is not fully characterised. We analysed these histopathological parameters and their relationships in rectal cancer patients who participated in a clinical trial of preoperative RT. One hundred and forty-eight preoperative biopsies and 153 surgically resected tumours were examined. Of the surgical specimens, 81 had surgery alone and 72 received RT before surgery. A higher grade of inflammatory infiltration was related to favourable survival in the whole group of patients (p=0.004, for multivariate analysis p=0.01) as well as in the subgroups of patients with (p=0.04) or without RT (p=0.01). After RT, tumours showed a decreased infiltration (p=0.0003) and increased necrosis (p=0.006), strong necrosis was related to favourable survival (p=0.046). Necrosis (p=0.054) and fibrosis (p=0.06) tended to be increased in p53-negative tumours after RT. Inflammatory infiltration was a strong prognostic factor in rectal cancer patients, regardless of RT. RT tended to induce necrosis and fibrosis in p53-negative tumours.

  • 20. Arlehag, L
    et al.
    Adell, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Knutsen Holmqvist, Annica
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Thorstenson, Sten
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology.
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    ATM expression in rectal cancers with or without preoperative radiotherapy2005In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 14, no 2, p. 313-317Article in journal (Refereed)
    Abstract [en]

    Patients with ATM (Ataxia-Telangiectasia mutated) mutation show increased sensitivity to radiation and have a higher risk of developing malignancies. The present study aimed to investigate whether ATM expression was related to radiotherapy, and clinicopathological and biological variables in rectal cancers. ATM expression was immunohistochemically examined in 78 rectal cancers from patients who participated in a Swedish rectal cancer trial of preoperative radiotherapy. Of 78 patients, 44 underwent surgery alone, and 34 underwent both preoperative radiotherapy and surgery. Fifty-eight cases had normal rectal mucosa adjacent to the tumour. The results showed that, compared to normal mucosa, tumours had less nuclear (p=0.03) but more cytoplasmic expression of ATM (p=0.004). In tumours, less expression of ATM, either in the nucleus (p=0.07) or in the cytoplasm (p=0.02 for staining intensity, and p=0.07 for staining percentage), tended to be correlated with male patients. Also, ATM expression was not related to radiotherapy or other clinicopathological and biological variables (p > 0.05). In conclusion, the pattern of ATM expression was changed from normal mucosa to tumour. Less expression of ATM may be related to males.

  • 21.
    Knutsen Holmqvist, Annica
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Adell, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Survivin expression is an independent prognostic factor in rectal cancer patients with and without preoperative radiotherapy2004In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 60, no 1, p. 149-155Article in journal (Refereed)
    Abstract [en]

    Purpose: Survivin, as an inhibitor of apoptosis, is undetectable in normal tissues but expressed in tumors. Survivin expression in rectal cancer patients who have undergone preoperative radiotherapy (RT) alone has not been studied. We analyzed the relationships of survivin expression to RT, clinicopathologic variables, apoptosis, and p53 expression in rectal cancer patients who participated in a trial of preoperative RT. Methods and Materials: Survivin was immunohistochemically examined in 98 rectal tumors (74 had adjacent normal mucosa). Of 98 patients, 57 underwent surgery alone and 41 underwent RT before surgery. Results: Survivin positivity was related to worse survival, independent of Dukes' stage, local and distant recurrence, differentiation, gender, age, apoptosis, and p53 expression (p = 0.02). Survivin was not associated with survival in the patients without (p = 0.08) or with (p = 0.19) RT. After RT, survivin tended to be increased in adjacent normal mucosa (p = 0.057) but not in tumors (p = 0.71). Conclusion: Survivin was independently related to survival in rectal cancer patients who participated in a trial of preoperative RT, but not in either treatment group (surgery alone or surgery plus RT). Whether the effect of survivin on tumors is associated with RT and further related to patient survival needs to be investigated in a larger number of patients. (C) 2004 Elsevier Inc.

  • 22. Knutsen Holmqvist, Annica
    et al.
    Adell, Gunnar
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Roman, M
    Nationall Board Forensic Medicine .
    Survivin expression is an independent prognostic factor in rectal cancer patients with and without preoperative radiotherapy2004In: Journal of chromatography. B, ISSN 1570-0232, E-ISSN 1873-376X, Vol. 60, no 1, p. 149-155Article in journal (Refereed)
    Abstract [en]

    Purpose: Survivin, as an inhibitor of apoptosis, is undetectable in normal tissues but expressed in tumors. Survivin expression in rectal cancer patients who have undergone preoperative radiotherapy (RT) alone has not been studied. We analyzed the relationships of survivin expression to RT, clinicopathologic variables, apoptosis, and p53 expression in rectal cancer patients who participated in a trial of preoperative RT. Methods and Materials: Survivin was immunohistochemically examined in 98 rectal tumors (74 had adjacent normal mucosa). Of 98 patients, 57 underwent surgery alone and 41 underwent RT before surgery. Results: Survivin positivity was related to worse survival, independent of Dukes' stage, local and distant recurrence, differentiation, gender, age, apoptosis, and p53 expression (p = 0.02). Survivin was not associated with survival in the patients without (p = 0.08) or with (p = 0.19) RT. After RT, survivin tended to be increased in adjacent normal mucosa (p = 0.057) but not in tumors (p = 0.71). Conclusion: Survivin was independently related to survival in rectal cancer patients who participated in a trial of preoperative RT, but not in either treatment group (surgery alone or surgery plus RT). Whether the effect of survivin on tumors is associated with RT and further related to patient survival needs to be investigated in a larger number of patients. (C) 2004 Elsevier Inc.

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