Incidence and management of patients with colorectal cancer and synchronous and metachronous colorectal metastases : a population-based study

Background This population-based study aimed to examine the incidence, patterns and results of multimodal management of metastatic colorectal cancer. Methods A retrospective population-based study was conducted on patients with metastatic colorectal cancer in Central Finland in 2000-2015. Clinical and histopathological data were retrieved and descriptive analysis was conducted to determine the pattern of metastatic disease, defined as synchronous, early metachronous (within 12 months of diagnosis of primary disease) and late metachronous (more than 12 months after diagnosis). Subgroups were compared for resection and overall survival (OS) rates. Results Of 1671 patients, 296 (17.7 per cent) had synchronous metastases, and 255 (19.6 per cent) of 1302 patients with resected stage I-III tumours developed metachronous metastases (94 early and 161 late metastases). Liver, pulmonary and intraperitoneal metastases were the most common sites. The commonest metastatic patterns were a combination of liver and lung metastases. The overall metastasectomy rate for patients with synchronous metastases was 16.2 per cent; in this subgroup, 3- and 5-year OS rates after any resection were 63 and 44 per cent respectively, compared with 7.1 and 3.3 per cent following no resection (P <0.001). The resection rate was higher for late than for early metachronous disease (28.0versus17 per cent respectively;P = 0.048). Three- and 5-year OS rates after any resection of metachronous metastases were 78 and 62 per cent respectivelyversus42.1 and 18.2 per cent with no metastasectomy (P <0.001). Similarly, 3- and 5-year OS rates after any metastasectomy for early metachronous metastases were 57 and 50 per centversus84 and 66 per cent for late metachronous metastases (P = 0.293). Conclusion The proportion of patients with metastatic colorectal cancer was consistent with that in earlier population-based studies, as were resection rates for liver and lung metastases and survival after resection. Differentiation between synchronous, early and late metachronous metastases can improve assessment of resectability and survival.Peer reviewe

Impact of Age and Comorbidity on Multimodal Management and Survival from Colorectal Cancer: A Population-Based Study

This retrospective population-based study examined the impact of age and comorbidity burden on multimodal management and survival from colorectal cancer (CRC). From 2000 to 2015, 1479 consecutive patients, who underwent surgical resection for CRC, were reviewed for age-adjusted Charlson comorbidity index (ACCI) including 19 well-defined weighted comorbidities. The impact of ACCI on multimodal management and survival was compared between low (score 0–2), intermediate (score 3) and high ACCI (score ≥ 4) groups. Changes in treatment from 2000 to 2015 were seen next to a major increase of laparoscopic surgery, increased use of adjuvant chemotherapy and an intensified treatment of metastatic disease. Patients with a high ACCI score were, by definition, older and had higher comorbidity. Major elective and emergency resections for colon carcinoma were evenly performed between the ACCI groups, as were laparoscopic and open resections. (Chemo)radiotherapy for rectal carcinoma was less frequently used, and a higher rate of local excisions, and consequently lower rate of major elective resections, was performed in the high ACCI group. Adjuvant chemotherapy and metastasectomy were less frequently used in the ACCI high group. Overall and cancer-specific survival from stage I-III CRC remained stable over time, but survival from stage IV improved. However, the 5-year overall survival from stage I–IV colon and rectal carcinoma was worse in the high ACCI group compared to the low ACCI group. Five-year cancer-specific and disease-free survival rates did not differ significantly by the ACCI. Cox proportional hazard analysis showed that high ACCI was an independent predictor of poor overall survival (p < 0.001). Our results show that despite improvements in multimodal management over time, old age and high comorbidity burden affect the use of adjuvant chemotherapy, preoperative (chemo)radiotherapy and management of metastatic disease, and worsen overall survival from CRC

Impact of Age and Comorbidity on Multimodal Management and Survival from Colorectal Cancer: A Population-Based Study

This retrospective population-based study examined the impact of age and comorbidity burden on multimodal management and survival from colorectal cancer (CRC). From 2000 to 2015, 1479 consecutive patients, who underwent surgical resection for CRC, were reviewed for age-adjusted Charlson comorbidity index (ACCI) including 19 well-defined weighted comorbidities. The impact of ACCI on multimodal management and survival was compared between low (score 0–2), intermediate (score 3) and high ACCI (score ≥ 4) groups. Changes in treatment from 2000 to 2015 were seen next to a major increase of laparoscopic surgery, increased use of adjuvant chemotherapy and an intensified treatment of metastatic disease. Patients with a high ACCI score were, by definition, older and had higher comorbidity. Major elective and emergency resections for colon carcinoma were evenly performed between the ACCI groups, as were laparoscopic and open resections. (Chemo)radiotherapy for rectal carcinoma was less frequently used, and a higher rate of local excisions, and consequently lower rate of major elective resections, was performed in the high ACCI group. Adjuvant chemotherapy and metastasectomy were less frequently used in the ACCI high group. Overall and cancer-specific survival from stage I-III CRC remained stable over time, but survival from stage IV improved. However, the 5-year overall survival from stage I–IV colon and rectal carcinoma was worse in the high ACCI group compared to the low ACCI group. Five-year cancer-specific and disease-free survival rates did not differ significantly by the ACCI. Cox proportional hazard analysis showed that high ACCI was an independent predictor of poor overall survival (p < 0.001). Our results show that despite improvements in multimodal management over time, old age and high comorbidity burden affect the use of adjuvant chemotherapy, preoperative (chemo)radiotherapy and management of metastatic disease, and worsen overall survival from CRC

Impact of Age and Comorbidity on Multimodal Management and Survival from Colorectal Cancer: A Population-Based Study

This retrospective population-based study examined the impact of age and comorbidity burden on multimodal management and survival from colorectal cancer (CRC). From 2000 to 2015, 1479 consecutive patients, who underwent surgical resection for CRC, were reviewed for age-adjusted Charlson comorbidity index (ACCI) including 19 well-defined weighted comorbidities. The impact of ACCI on multimodal management and survival was compared between low (score 0-2), intermediate (score 3) and high ACCI (score >= 4) groups. Changes in treatment from 2000 to 2015 were seen next to a major increase of laparoscopic surgery, increased use of adjuvant chemotherapy and an intensified treatment of metastatic disease. Patients with a high ACCI score were, by definition, older and had higher comorbidity. Major elective and emergency resections for colon carcinoma were evenly performed between the ACCI groups, as were laparoscopic and open resections. (Chemo)radiotherapy for rectal carcinoma was less frequently used, and a higher rate of local excisions, and consequently lower rate of major elective resections, was performed in the high ACCI group. Adjuvant chemotherapy and metastasectomy were less frequently used in the ACCI high group. Overall and cancer-specific survival from stage I-III CRC remained stable over time, but survival from stage IV improved. However, the 5-year overall survival from stage I-IV colon and rectal carcinoma was worse in the high ACCI group compared to the low ACCI group. Five-year cancer-specific and disease-free survival rates did not differ significantly by the ACCI. Cox proportional hazard analysis showed that high ACCI was an independent predictor of poor overall survival (p < 0.001). Our results show that despite improvements in multimodal management over time, old age and high comorbidity burden affect the use of adjuvant chemotherapy, preoperative (chemo)radiotherapy and management of metastatic disease, and worsen overall survival from CRC

Medico-legal autopsy in postoperative hemodynamic collapse following coronary artery bypass surgery

Sudden unexpected postoperative hemodynamic collapse with a high mortality develops in 1–3% of patients undergoing coronary artery bypass surgery (CABG). The contribution of surgical graft complications to this serious condition is poorly known and their demonstration at autopsy is a challenging task. Isolated CABG was performed in 8,807 patients during 1988–1999. Of the patients, 76 (0.9%) developed sudden postoperative hemodynamic collapse resulting in subsequent emergency reopening of the median sternotomy and open cardiac massage. Further emergency reoperation could be performed in 62 (82%) whereas 14 patients died prior to reoperation and a further 21 did not survive the reoperation or died a few days later. All 35 (46%) patients who did not survive were subjected to medico-legal autopsy combined with postmortem cast angiography. By combining clinical data with autopsy and angiography data, various types of graft complications were observed in 27 (36%, 1.3 per patient) of the 76 patients with hemodynamic collapse. There were no significant differences in the frequency (33 vs. 40%) or number of complicated grafts per patient (1.2 vs. 1.4) between those who survived reoperation and who did not. Autopsy detected 25 major and minor findings not diagnosed clinically. Postmortem cast angiography visualized 2 graft twists not possible to detect by autopsy dissection only. Surgical graft complications were the most frequent single cause for sudden postoperative hemodynamic collapse in CABG patients leading to a fatal outcome in almost half of the cases. Postmortem angiography improved the accuracy of autopsy diagnostics of graft complications

CD3+ and CD8+ T-Cell-Based Immune Cell Score and PD-(L)1 Expression in Pulmonary Metastases of Microsatellite Stable Colorectal Cancer

The objective of this study was to evaluate the prognostic value of CD3+ and CD8+ based immune cell score (ICS), programmed death -1 (PD-1) and programmed death ligand -1 (PD-L1) in pulmonary metastases of proficient mismatch repair colorectal cancer (CRC) patients. A total of 101 pulmonary metastases and 62 primary CRC tumours were stained for CD3+, CD8+, PD-1 and PD-L1 expression. The prognostic value of ICS, PD-1/PD-L1 expression in 67 first pulmonary metastases and 61 primary CRC tumour was analysed. Comparative analysis was also performed between primary tumours and pulmonary metastases, as well as between T-cell densities and PD-1/PD-L1 expression. The 5-year overall survival rates of low, intermediate, and high ICS in pulmonary metastases were 10.0%, 25.5% and 47.0% (p = 0.046), respectively. Patients with high vs. low ICS in pulmonary metastases had a significantly better 5-year survival (adjusted HR 0.25, 95% CI 0.09-0.75, p = 0.013). High tumour cell PD-L1 expression in the pulmonary metastases was associated with improved survival (p = 0.024). Primary tumour CD8+ expression was significantly correlated with all T-cell densities in pulmonary metastases. Conclusion: The ICS evaluated from the resected pulmonary metastases of CRC showed significant prognostic value. High PD-L1 expression in pulmonary metastases is associated with favourable prognosis.publishedVersionPeer reviewe

Use of psychotropic drugs before pregnancy and the risk for induced abortion: population-based register-data from Finland 1996-2006

<p>Abstract</p> <p>Background</p> <p>Some, though not all studies have reported an increased risk for mental health problems after an induced abortion. Problems with design and data have compromised these studies and the generalisation of their results.</p> <p>Methods</p> <p>The Finnish Medication and Pregnancy database (N = 622 671 births and 114 518 induced abortions for other than fetal reasons) in 1996-2006 was utilised to study the use of psychotropic drugs in the three months before a pregnancy ending in a birth or an induced abortion.</p> <p>Results</p> <p>In total 2.1% of women with a birth and 5.1% of women with an induced abortion had used a psychotropic medicine 0-3 months before pregnancy. Psychotropic drug users terminated their pregnancies (30.9%) more often than other pregnant women (15.5%). Adjustment for background characteristics explained one third of this elevated risk, but the risk remained significantly increased among users of psychotropic medicine (OR 1.94, 95% confidence intervals 1.87-2.02). A similar risk was found for first pregnancies (30.1% vs. 18.9%; adjusted OR 1.53, 95% confidence intervals 1.42-1.65). The rate for terminating pregnancy was the highest for women using hypnotics and sedatives (35.6% for all pregnancies and 29.1% for first pregnancies), followed by antipsychotics (33.9% and 36.0%) and antidepressants (32.0% and 32.1%).</p> <p>Conclusions</p> <p>The observed increased risk for induced abortion among women with psychotropic medication highlighs the importance to acknowledge the mental health needs of women seeking an induced abortion. Further studies are needed to establish the impact of pre-existing differences in mental health on mental health outcomes of induced abortions compared to outcomes of pregnancies ending in a birth.</p

Understanding the prescription of antidepressants: a Qualitative study among French GPs

<p>Abstract</p> <p>Background</p> <p>One-tenth of France's population is prescribed at least one antidepressant, primarily by General Practitioners. The reasons for this high prescription rate remain unclear. One-third of these prescriptions may not comply with clinical practice guidelines, and 20% are potentially unrelated to any psychiatric condition. Our aim was to explore how GPs declare they use antidepressants in daily practice and understand their reasons for prescribing them.</p> <p>Method</p> <p>Six focus groups including a total of 56 rural and urban GPs, with four interviews were performed. The topic guide focused on reasons for prescribing antidepressants in various primary care situations. Phenomenological analysis was performed by four researchers.</p> <p>Results</p> <p>Antidepressants were seen as useful and not harmful. Personal assessment based on experience and feeling determined the GPs' decisions rather than the use of scales. Twenty-four "non-psychiatric" conditions possibly leading to prescription of antidepressants in primary care were found.</p> <p>Conclusions</p> <p>The GPs reported prescribing antidepressants for a wide range of conditions other than depression. The GPs' decision making process is difficult and complex. They seemed to prefer to focus on their difficulties in diagnosing depression rather than on useless overtreatment. Instead of using the guidelines criteria to detect potential cases of useful prescription, physicians tend to use their own tools based on gut feelings, knowledge of the patient and contextual issues.</p

Long-Term Survival After Transhiatal Versus Transthoracic Esophagectomy: A Population-Based Nationwide Study in Finland

Background No population-based studies comparing long-term survival after transhiatal esophagectomy (THE) and transthoracic esophagectomy (TTE) exist. This study aimed to compare the 5-year survival of esophageal cancer patients undergoing THE or TTE in a population-based nationwide setting. Methods This study included all curatively intended THE and TTE for esophageal cancer in Finland during 1987-2016, with follow-up evaluation until 31 December 2019. Cox proportional hazard models provided hazard ratios (HRs) with 95% confidence intervals (CIs) of 5-year and 90-day mortality. The results were adjusted for age, sex, year of operation, comorbidities, histology, neoadjuvant treatment, and pathologic stage. Results A total of 1338 patients underwent THE (n = 323) or TTE (n = 1015). The observed 5-year survival rate was 39.3% after THE and 45.0% after TTE (p = 0.072). In adjusted model 1, THE was not associated with greater 5-year mortality (HR 0.99; 95% CI 0.82-1.20) than TTE. In adjusted model 2, including T stage instead of pathologic stage, the 5-year mortality hazard rates after THE (HR 0.87, 95% CI 0.72-1.05) and TTE were comparable. The 90-day mortality rate for THE was higher than for TTE (adjusted HR 0.72; 95% CI 0.45-1.14). In subgroup analyses, no differences between THE and TTE were observed in Siewert II gastroesophageal junction cancers, esophageal cancers, or pN0 tumors, nor in the comparison of THE and TTE with two-field lymphadenectomy. The sensitivity analysis, including patients with missing patient records, who underwent surgery during 1996-2016 mirrored the main analysis. Conclusions This Finnish population-based nationwide study suggests no difference in 5-year or 90-day mortality after THE and TTE for esophageal cancer.</p

Multiplexed analysis of macrophage polarisation in pulmonary metastases of microsatellite stable colorectal cancer

Tumour-associated macrophages (TAMs) express a continuum of phenotypes ranging from an anti-tumoural M1-like phenotype to a pro-tumoural M2-like phenotype. During cancer progression, TAMs may shift to a more M2-like polarisation state, but the role of TAMs in CRC metastases is unclear. We conducted a comprehensive spatial and prognostic analysis of TAMs in CRC pulmonary metastases and corresponding primary tumours using multiplexed immunohistochemistry and machine learning-based image analysis. We obtained data from 106 resected pulmonary metastases and 74 corresponding primary tumours. TAMs in the resected pulmonary metastases were located closer to the cancer cells and presented a more M2-like polarised state in comparison to the primary tumours. Higher stromal M2-like macrophage densities in the invasive margin of pulmonary metastases were associated with worse 5-year overall survival (HR 3.19, 95% CI 1.35–7.55, p = 0.008). The results of this study highlight the value of multiplexed analysis of macrophage polarisation in cancer metastases and might have clinical implications in future cancer therapy.Peer reviewe