Research letter : Oncological treatment reported by the Finnish Cancer Registry compared to given neoadjuvant treatment in patients undergoing esophagectomy for cancer-A nationwide study

Peer reviewe

Preoperative hemoglobin count and prognosis of esophageal cancer, a population-based nationwide study in Finland

BackgroundThe prognostic value of preoperative hemoglobin in patients undergoing esophagectomy is unknown. The aim of this study was to examine whether preoperative hemoglobin is associated with prognosis in patients undergoing esophagectomy for cancer.Materials and methodsThis was a population-based nationwide retrospective cohort study in Finland, using Finnish National Esophago-Gastric Cancer Cohort (FINEGO). Esophagectomy patients with available preoperative hemoglobin measurement were included. Multivariable cox regression provided hazard ratios (HR) with 95% confidence intervals (CI), adjusted for calendar period of surgery, age at surgery, sex, comorbidity (Charlson Comorbidity Index), tumor histology, tumor stage, neoadjuvant therapy, type of surgery (minimally invasive or open) and annual hospital volume.ResultsOf the 1313 patients, 932 (71.0%) were men and 799 (60.9%) had esophageal adenocarcinoma. Overall all-cause mortality was significantly higher in the lowest hemoglobin count tertile (HR 1.26 (1.07–1.47)) compared to the highest tertile, but this association was attenuated after adjustment for confounding. No differences were found between the preoperative hemoglobin groups in the adjusted analyses of 90-day all-cause, 5-year all-cause, and 5-year cancer-specific mortality.ConclusionIn this population-based nationwide study, preoperative hemoglobin count had no independent prognostic significance in esophageal cancer.KeywordsHemoglobin; Esophageal cancer; Esophagectomy; Mortality; Prognosis</p

Ruokatorvisyövän hoito kehittyy

Vertaisarvioitu. English summaryPeer reviewe

Incidence and Mortality in Upper Gastrointestinal Cancer After Negative Endoscopy for Gastroesophageal Reflux Disease

BACKGROUND AND AIMS: Gastroesophageal reflux disease (GERD) is associated with an increased risk of cancer of the upper gastrointestinal tract. This study aimed to assess whether and to what extent a negative upper endoscopy in patients with GERD is associated with decreased incidence and mortality in upper gastrointestinal cancer (ie, esophageal, gastric, or duodenal cancer). METHODS: We conducted a population-based cohort study of all patients with newly diagnosed GERD between July 1, 1979 and December 31, 2018 in Denmark, Finland, Norway, and Sweden. The exposure, negative upper endoscopy, was examined as a time-varying exposure, where participants contributed unexposed person-time from GERD diagnosis until screened and exposed person-time from the negative upper endoscopy. The incidence and mortality in upper gastrointestinal cancer were assessed using parametric flexible models, providing adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Among 1,062,740 patients with GERD (median age 58 years; 52% were women) followed for a mean of 7.0 person-years, 5324 (0.5%) developed upper gastrointestinal cancer and 4465 (0.4%) died from such cancer. Patients who had a negative upper endoscopy had a 55% decreased risk of upper gastrointestinal cancer compared with those who did not undergo endoscopy (HR, 0.45; 95% CI, 0.43-0.48), a decrease that was more pronounced during more recent years (HR, 0.34; 95% CI, 0.30-0.38 from 2008 onward), and was otherwise stable across sex and age groups. The corresponding reduction in upper gastrointestinal mortality among patients with upper endoscopy was 61% (adjusted HR, 0.39; 95% CI, 0.37-0.42). The risk reduction after a negative upper endoscopy in incidence and mortality lasted for 5 and at least 10 years, respectively. CONCLUSIONS: Negative upper endoscopy is associated with strong and long-lasting decreases in incidence and mortality in upper gastrointestinal cancer in patients with GERD.Peer reviewe

Toisiolaki - lääketieteellisen tutkimuksen mahdollistaja vai tukahduttaja?

Lähtökohdat : Suomessa tuli 1.5.2019 voimaan niin sanottu toisiolaki eli Laki sosiaali- ja terveys­tietojen toissijaisesta käytöstä. Kyselytutkimuksemme tarkoitus oli selvittää kliinikkotutkijoiden kokemuksia toisiolain vaikutuksista ja käytännön toteutuksesta. Menetelmät : Suomalaisia kliinikkotutkijoita pyydettiin arvioimaan Webropol-alustalla toisiolain aiheuttamia aikataulumuutoksia, talousvaikutuksia, tutkimusyhteistyössä tapahtuneita muutoksia, mahdollisia esteitä ja hyötyjä lain voimaantuloon liittyen sekä muita lain aiheuttamia positiivisia ja negatiivisia vaikutuksia. Tulokset : Vastaajista (n = 430) 64,4 % raportoi, että tutkimustoiminnan kustannukset ovat nousseet toisiolain mukana. Vastaajista 38,4–45,6 % oli jättänyt tutkimusprojekteja käynnistämättä joko lupahakemuksen hinnan tai etäkäyttöympäristön kustannusten sekä sen käyttövaatimuksen vuoksi. Päätelmät :Tutkimuksemme perusteella on syytä epäillä, että toisiolain soveltaminen vaikuttaa heikentävästi julkaisujen määrään ja laatuun ja heikentää Suomen kilpailukykyä etenkin tutkija­lähtöisessä tutkimuksessa. Toisiolain seuraukset kohdistuvat erityisesti suomalaisiin potilaisiin, heidän hoitonsa laatuun sekä hoidon tasavertaisuuteen.publishedVersionPeer reviewe

Toisiolaki - lääketieteellisen tutkimuksen mahdollistaja vai tukahduttaja?

Vertaisarvioitu.Lähtökohdat : Suomessa tuli 1.5.2019 voimaan niin sanottu toisiolaki eli Laki sosiaali- ja terveys¬tietojen toissijaisesta käytöstä. Kyselytutkimuksemme tarkoitus oli selvittää kliinikkotutkijoiden kokemuksia toisiolain vaikutuksista ja käytännön toteutuksesta. Menetelmät : Suomalaisia kliinikkotutkijoita pyydettiin arvioimaan Webropol-alustalla toisiolain aiheuttamia aikataulumuutoksia, talousvaikutuksia, tutkimusyhteistyössä tapahtuneita muutoksia, mahdollisia esteitä ja hyötyjä lain voimaantuloon liittyen sekä muita lain aiheuttamia positiivisia ja negatiivisia vaikutuksia. Tulokset : Vastaajista (n = 430) 64,4 % raportoi, että tutkimustoiminnan kustannukset ovat nousseet toisiolain mukana. Vastaajista 38,4–45,6 % oli jättänyt tutkimusprojekteja käynnistämättä joko lupahakemuksen hinnan tai etäkäyttöympäristön kustannusten sekä sen käyttövaatimuksen vuoksi. Päätelmät :Tutkimuksemme perusteella on syytä epäillä, että toisiolain soveltaminen vaikuttaa heikentävästi julkaisujen määrään ja laatuun ja heikentää Suomen kilpailukykyä etenkin tutkija¬lähtöisessä tutkimuksessa. Toisiolain seuraukset kohdistuvat erityisesti suomalaisiin potilaisiin, heidän hoitonsa laatuun sekä hoidon tasavertaisuuteen.Peer reviewe

The interplay of matrix metalloproteinase-8, transforming growth factor-beta 1 and vascular endothelial growth factor-C cooperatively contributes to the aggressiveness of oral tongue squamous cell carcinoma

Background: Matrix metalloproteinase-8 (MMP-8) has oncosuppressive properties in various cancers. We attempted to assess MMP-8 function in oral tongue squamous cell carcinoma (OTSCC). Methods: MMP-8 overexpressing OTSCC cells were used to study the effect of MMP-8 on proliferation, apoptosis, migration, invasion and gene and protein expression. Moreover, MMP-8 functions were assessed in the orthotopic mouse tongue cancer model and by immunohistochemistry in patient samples. Results: MMP-8 reduced the invasion and migration of OTSCC cells and decreased the expression of MMP-1, cathepsin-K and vascular endothelial growth factor-C (VEGF-C). VEGF-C was induced by transforming growth factor-beta 1 (TGF-beta 1) in control cells, but not in MMP-8 overexpressing cells. In human OTSCC samples, low MMP-8 in combination with high VEGF-C was an independent predictor of poor cancer-specific survival. TGF-beta 1 treatment also restored the migration of MMP-8 overexpressing cells to the level of control cells. In mouse tongue cancer, MMP-8 did not inhibit metastasis, possibly because it was eliminated in the peripheral carcinoma cells. Conclusions: The suppressive effects of MMP-8 in OTSCC may be mediated through interference of TGF-beta 1 and VEGF-C function and altered proteinase expression. Together, low MMP-8 and high VEGF-C expression have strong independent prognostic value in OTSCC.Peer reviewe

Small oral tongue cancers (ae 4 cm in diameter) with clinically negative neck : from the 7th to the 8th edition of the American Joint Committee on Cancer

One of the main changes in the 8th edition of the American Joint Committee on Cancer (AJCC) for staging of oral cancer is the inclusion of depth of invasion (DOI) in the T category. However, cancers in different oral subsites have variable behavior, with oral tongue squamous cell carcinoma (OTSCC) being the most aggressive one even at early stage. Thus, it is necessary to evaluate the performance of this new T category in homogenous cohort of early OTSCC. Therefore, we analyzed a large cohort of patients with a small (ae4 cm) OTSCC to demonstrate the differences in T stage between the AJCC 7th and 8th editions. A total of 311 early-stage cases (AJCC 7th) of OTSCC were analyzed. We used 5 mm and 10 mm DOI for upstaging from T1 to T2 and from T2 to T3 respectively, as in the AJCC 8th. We further reclassified the cases according to our own proposal suggesting 2 mm to upstage to T2 and 4 mm to upstage to T3. According to AJCC 7th, there were no significant differences in the survival analysis. When we applied the 8th edition, many cases were upstaged to T3 and thus associated with worse disease-specific survival (HR 2.37, 95% CI 1.12-4.99) and disease-free survival (HR 2.12, 95% CI 1.09-4.08). Based on our proposal, T3 cases were associated with even worse disease-specific survival (HR 4.19, 95% CI 2.27-7.74). The 8th edition provides better survival prediction for OTSCC than the 7th and can be further optimized by lowering the DOI cutoffs.Peer reviewe

Tenascin-C and fibronectin expression divide early stage tongue cancer into low- and high-risk groups

Background:Oral tongue squamous cell carcinoma (OTSCC) metastasises early, especially to regional lymph nodes. There is an ongoing debate on which early stage (T1-T2N0) patients should be treated with elective neck dissection. We need prognosticators for early stage tongue cancer. Methods: Mice immunisation with human mesenchymal stromal cells resulted in production of antibodies against tenascin-C (TNC) and fibronectin (FN), which were used to stain 178 (98 early stage), oral tongue squamous cell carcinoma samples. TenascinC and FN expression in the stroma (negative, moderate or abundant) and tumour cells (negative or positive) were assessed. Similar staining was obtained using corresponding commercial antibodies. Results: Expression of TNC and FN in the stroma, but not in the tumour cells, proved to be excellent prognosticators both in all stages and in early stage cases. Among early stages, when stromal TNC was negative, the 5-year survival rate was 88%. Correspondingly, when FN was negative, no cancer deaths were observed. Five-year survival rates for abundant expression of TNC and FN were 43% and 25%, respectively. Conclusions: Stromal TNC and, especially, FN expressions differentiate patients into low-and high-risk groups. Surgery alone of early stage primary tumours might be adequate when stromal FN is negative. Aggressive treatments should be considered when both TNC and FN are abundant.Peer reviewe