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3. Truncating NFKB1 variants cause combined NLRP3 inflammasome activation and type I interferon signaling and predispose to necrotizing fasciitis

Author

Nurmi, Katariina, Silventoinen, Kristiina, Keskitalo, Salla, Rajamäki, Kristiina, Kouri, Vesa-Petteri, Kinnunen, Matias, Jalil, Sami, Maldonado, Rocio, Wartiovaara, Kirmo, Nievas, Elma Inés, Denita-Juárez, Silvina Paola, Duncan, Christopher J.A., Kuismin, Outi, Saarela, Janna, Romo, Inka, Martelius, Timi, Parantainen, Jukka, Beklen, Arzu, Bilicka, Marcelina, Matikainen, Sampsa, Nordström, Dan C., Kaustio, Meri, Wartiovaara-Kautto, Ulla, Kilpivaara, Outi, Klein, Christoph, Hauck, Fabian, Jahkola, Tiina, Hautala, Timo, Varjosalo, Markku, Barreto, Goncalo, Seppänen, Mikko R.J., and Eklund, Kari K.

Published
2024
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6. Regarding: Predicting Regional Lymph Node Recurrence in The Modern Age of Tumor-Positive Sentinel Node Melanoma

Author

Thompson, John F., Hyngstrom, John, Caracò, Corrado, Zager, Jonathan S., Jahkola, Tiina, Bowles, Tawnya L., Pennacchioli, Elisabetta, Hoekstra, Harald J., Moncrieff, Marc, Ingvar, Christian, van Akkooi, Alexander, Sabel, Michael S., Levine, Edward A., Henderson, Michael, Dummer, Reinhard, Rossi, Carlo Riccardo, Kane, 3rd, John M., Trocha, Steven, Wright, Frances, Byrd, David R., Matter, Maurice, MacKenzie-Ross, Alastair, Kelley, Mark C., Terheyden, Patrick, Huston, Tara L., Wayne, Jeffrey D., Neuman, Heather, Smithers, B. Mark, Desai, Darius, Gershenwald, Jeffrey E., Schneebaum, Shlomo, Gesierich, Anja, Jacobs, Lisa K., Lewis, James M., O’Donoghue, Cristina, Sardi, Armando, McKinnon, J. Greg, Slingluff, Craig L., Farma, Jeffrey M., Schultz, Erwin, Scheri, Randall P., Vidal-Sicart, Sergi, Testori, Alessandro A. E., Scolyer, Richard A., Elashoff, David E., Cochran, Alistair J., and Faries, Mark B.

Published
2023
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14. Regarding: Predicting Regional Lymph Node Recurrence in The Modern Age of Tumor-Positive Sentinel Node Melanoma

Author

Thompson, John F, Hyngstrom, John, Caracò, Corrado, Zager, Jonathan S, Jahkola, Tiina, Bowles, Tawnya L, Pennacchioli, Elisabetta, Hoekstra, Harald J, Moncrieff, Marc, Ingvar, Christian, van Akkooi, Alexander, Sabel, Michael S, Levine, Edward A, Henderson, Michael, Dummer, Reinhard, Rossi, Carlo Riccardo, Kane, John M, Trocha, Steven, Wright, Frances, Byrd, David R, Matter, Maurice, MacKenzie-Ross, Alastair, Kelley, Mark C, Terheyden, Patrick, Huston, Tara L, Wayne, Jeffrey D, Neuman, Heather, Smithers, B Mark, Desai, Darius, Gershenwald, Jeffrey E, et al, and University of Zurich

Subjects
Oncology, 10177 Dermatology Clinic, 610 Medicine & health, 2730 Oncology, Surgery, 2746 Surgery
Published
2023

24. Pelvic sentinel lymph nodes have minimal impact on survival in melanoma patients

Author

Vuoristo, Mikko, Muhonen, Timo, Koljonen, Virve, Juteau, Susanna, Hernberg, Micaela, Ilmonen, Suvi, Jahkola, Tiina, HUS Musculoskeletal and Plastic Surgery, Plastiikkakirurgian yksikkö, Clinicum, Department of Oncology, University of Helsinki, HUS Comprehensive Cancer Center, Department of Surgery, Department of Pathology, and HUSLAB

Subjects
Skin Neoplasms, AcademicSubjects/MED00910, Bjs/2, 3126 Surgery, anesthesiology, intensive care, radiology, body regions, Lymphatic Metastasis, Humans, Lymph Node Excision, Original Article, Lymph Nodes, Sentinel Lymph Node, AcademicSubjects/MED00010, Melanoma, Retrospective Studies
Abstract

Background Lower limb or trunk melanoma often presents with femoral and pelvic sentinel lymph nodes (SLNs). The benefits of harvesting pelvic lymph nodes remain controversial. In this retrospective study, the frequency and predictors of pelvic SLNs (PSLNs), and the impact of PSLNs on survival and staging was investigated. Methods Altogether 285 patients with cutaneous melanoma located in the lower limb or trunk underwent sentinel lymph node biopsy of the inguinal/iliac lymph node basin at Helsinki University Hospital from 2009–2013. Patient characteristics, detailed pathology reports and follow-up data were retrieved from hospital files. Subgroups of patients categorized by presence of PSLNs were compared for outcome parameters including progression-free survival, melanoma-specific survival and groin recurrence. Results Superficial femoral/inguinal SLNs were present in all patients and 199 (69.8 per cent) also had PSLNs removed. Median number of SLNs per patient was five and median number of PSLNs was two. Sixty-three patients (22.1 per cent) had metastases in their SLNs and seven (2.5 per cent) had metastases in PSLNs. A single patient had metastases solely in PSLNs, while superficial SLNs remained negative. Harvesting PSLNs or the number of PSLNs retrieved had no impact on progression-free survival or overall survival. The removal of PSLNs did not affect the risk of postoperative seroma or lymphoedema. The only predictor of positive PSLNs was radioactivity count equal to or more than that of the hottest superficial SLNs. Conclusion Pelvic SLNs have minimal clinical impact on the outcome of melanoma patients especially in cases with negative superficial femoral/inguinal SLNs. Removal of PSLNs should be considered when they are the most radioactive nodes or equal to the hottest superficial femoral/inguinal SLNs in lymphoscintigraphy or during surgery. Preliminary results were presented in part at the International Sentinel Node Society Biennial Meeting, Tokyo, Japan, 11–13 October 2018., There is no consensus regarding the management of sentinel lymph nodes located in the pelvis in melanoma patients. In this study, the outcomes of 285 melanoma patients who underwent sentinel lymph node biopsy of the inguinal/iliac lymph node basin were analysed. Pelvic sentinel lymph nodes had minimal impact on survival and staging of melanoma patients, and removal of pelvic sentinel lymph nodes may be considered when they are the most radioactive nodes in lymphoscintigraphy or during surgery.

Published
2021

29. Rintarekonstruktio perustuu moniammatilliseen rintasyövän hoidon kokonaissuunnitteluun ja omakudossiirteiden käyttöön

Author

Jahkola, Tiina, Kolehmainen, Maija, Suominen, Sinikka, Svarvar, Catarina, Kauhanen, Susanna, Clinicum, Kirurgian osasto, Plastiikkakirurgian yksikkö, HUS Tukielin- ja plastiikkakirurgia, HUS Syöpäkeskus, and II kirurgian klinikka

Subjects
3122 Syöpätaudit, 3126 Kirurgia, anestesiologia, tehohoito, radiologia
Abstract

Vertaisarvioitu. Rintarekonstruktion asema osana kokonaisvaltaista rintasyövän hoitoa on Suomessa vakiintunut. Usein tehdään rintaa säästävä leikkaus, mutta 30-40 % naisista menettää rintansa rintasyöpäleikkauksessa. Rinnan puuttuminen tai merkittävä rintojen kokoero aiheuttavat toiminnallista haittaa, mikä oikeuttaa rekonstruktion. Rintarekonstruktio voidaan tehdä rinnan poiston yhteydessä tai vasta myöhäisvaiheessa. Rintaa voidaan korjata potilaan omalla eli autologisella kudoksella, keinomateriaalein tai menetelmiä yhdistelemällä. Suomessa on käytetty paljon alavatsa- ja selkäkielekettä. Rintaimplantit ja vapaa rasvasiirre ovat itsenäisiä tai täydentäviä tekniikoita. Rintarekonstruktion suunnittelussa potilaan terveydentilan, vartalon muodon ja toiveiden lisäksi ensisijaisen tärkeää on, että syövän hoidon kokonaisuus ei vaarannu. Onkologiset hoidot ovat harvoin este välittömälle rintarekonstruktiolle, kun se suunnitellaan moniammatillisessa tiimissä.

Published
2021

31. Therapeutic Value of Sentinel Lymph Node Biopsy in Patients With Melanoma: A Randomized Clinical Trial.

Author

Crystal, Jessica S., Thompson, John F., Hyngstrom, John, Caracò, Corrado, Zager, Jonathan S., Jahkola, Tiina, Bowles, Tawnya L., Pennacchioli, Elisabetta, Beitsch, Peter D., Hoekstra, Harald J., Moncrieff, Marc, Ingvar, Christian, van Akkooi, Alexander, Sabel, Michael S., Levine, Edward A., Agnese, Doreen, Henderson, Michael, Dummer, Reinhard, Neves, Rogerio I., and Rossi, Carlo Riccardo

Published
2022
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44. Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma

Author

Faries, Mark B., primary, Thompson, John F., additional, Cochran, Alistair J., additional, Andtbacka, Robert H., additional, Mozzillo, Nicola, additional, Zager, Jonathan S., additional, Jahkola, Tiina, additional, Bowles, Tawnya L., additional, Testori, Alessandro, additional, Beitsch, Peter D., additional, Hoekstra, Harald J., additional, Moncrieff, Marc, additional, Ingvar, Christian, additional, Wouters, Michel W.J.M., additional, Sabel, Michael S., additional, Levine, Edward A., additional, Agnese, Doreen, additional, Henderson, Michael, additional, Dummer, Reinhard, additional, Rossi, Carlo R., additional, Neves, Rogerio I., additional, Trocha, Steven D., additional, Wright, Frances, additional, Byrd, David R., additional, Matter, Maurice, additional, Hsueh, Eddy, additional, MacKenzie-Ross, Alastair, additional, Johnson, Douglas B., additional, Terheyden, Patrick, additional, Berger, Adam C., additional, Huston, Tara L., additional, Wayne, Jeffrey D., additional, Smithers, B. Mark, additional, Neuman, Heather B., additional, Schneebaum, Schlomo, additional, Gershenwald, Jeffrey E., additional, Ariyan, Charlotte E., additional, Desai, Darius C., additional, Jacobs, Lisa, additional, McMasters, Kelly M., additional, Gesierich, Anja, additional, Hersey, Peter, additional, Bines, Steven D., additional, Kane, John M., additional, Barth, Richard J., additional, McKinnon, Gregory, additional, Farma, Jeffrey M., additional, Schultz, Erwin, additional, Vidal-Sicart, Sergi, additional, Hoefer, Richard A., additional, Lewis, James M., additional, Scheri, Randall, additional, Kelley, Mark C., additional, Nieweg, Omgo E., additional, Noyes, R. Dirk, additional, Hoon, Dave S.B., additional, Wang, He-Jing, additional, Elashoff, David A., additional, and Elashoff, Robert M., additional

Published
2017
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45. Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma.

Author

Faries, Mark B., Thompson, John F., Cochran, Alistair J., Andtbacka, Robert H., Mozzillo, Nicola, Zager, Jonathan S., Jahkola, Tiina, Bowles, Tawnya L., Testori, Alessandro, Beitsch, Peter D., Hoekstra, Harald J., Moncrieff, Marc, Ingvar, Christian, Wouters, Michel W.J.M., Sabel, Michael S., Levine, Edward A., Agnese, Doreen, Henderson, Michael, Dummer, Reinhard, Rossi, Carlo R., Neves, Rogerio I., Trocha, Steven D., Wright, Frances, Byrd, David R., Matter, Maurice, Hsueh, Eddy, MacKenzie-Ross, Alastair, Johnson, Douglas B., Terheyden, Patrick, Berger, Adam C., Huston, Tara L., Wayne, Jeffrey D., Smithers, B. Mark, Neuman, Heather B., Schneebaum, Schlomo, Gershenwald, Jeffrey E., Ariyan, Charlotte E., Desai, Darius C., Jacobs, Lisa, McMasters, Kelly M., Gesierich, Anja, Hersey, Peter, Bines, Steven D., Kane, John M., Barth, Richard J., McKinnon, Gregory, Farma, Jeffrey M., Schultz, Erwin, Vidal-Sicart, Sergi, Hoefer, Richard A., Lewis, James M, Scheri, Randall, Kelley, Mark C., Nieweg, Omgo E., Noyes, R. Dirk, Hoon, Dave S.B., Wang, He-Jing, Elashoff, David A., Elashoff, Robert M., Faries, Mark B., Thompson, John F., Cochran, Alistair J., Andtbacka, Robert H., Mozzillo, Nicola, Zager, Jonathan S., Jahkola, Tiina, Bowles, Tawnya L., Testori, Alessandro, Beitsch, Peter D., Hoekstra, Harald J., Moncrieff, Marc, Ingvar, Christian, Wouters, Michel W.J.M., Sabel, Michael S., Levine, Edward A., Agnese, Doreen, Henderson, Michael, Dummer, Reinhard, Rossi, Carlo R., Neves, Rogerio I., Trocha, Steven D., Wright, Frances, Byrd, David R., Matter, Maurice, Hsueh, Eddy, MacKenzie-Ross, Alastair, Johnson, Douglas B., Terheyden, Patrick, Berger, Adam C., Huston, Tara L., Wayne, Jeffrey D., Smithers, B. Mark, Neuman, Heather B., Schneebaum, Schlomo, Gershenwald, Jeffrey E., Ariyan, Charlotte E., Desai, Darius C., Jacobs, Lisa, McMasters, Kelly M., Gesierich, Anja, Hersey, Peter, Bines, Steven D., Kane, John M., Barth, Richard J., McKinnon, Gregory, Farma, Jeffrey M., Schultz, Erwin, Vidal-Sicart, Sergi, Hoefer, Richard A., Lewis, James M, Scheri, Randall, Kelley, Mark C., Nieweg, Omgo E., Noyes, R. Dirk, Hoon, Dave S.B., Wang, He-Jing, Elashoff, David A., and Elashoff, Robert M.

Abstract

BACKGROUND: Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear. METHODS: In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis. RESULTS: Immediate completion lymph-node dissection was not associated with increased melanoma-specific survival among 1934 patients with data that could be evaluated in an intention-to-treat analysis or among 1755 patients in the per-protocol analysis. In the per-protocol analysis, the mean (±SE) 3-year rate of melanoma-specific survival was similar in the dissection group and the observation group (86±1.3% and 86±1.2%, respectively; P=0.42 by the log-rank test) at a median follow-up of 43 months. The rate of disease-free survival was slightly higher in the dissection group than in the observation group (68±1.7% and 63±1.7%, respectively; P=0.05 by the log-rank test) at 3 years, based on an increased rate of disease control in the regional nodes at 3 years (92±1.0% vs. 77±1.5%; P CONCLUSIONS: Immediate completion lymph-node dissection increased the rate of regional disease control and provided prognostic information but did not increase melanoma-specific survival among patients with melanoma and sentinel-node metastases. (Funded by the National Cancer Institute and others; MSLT-II ClinicalTrials.gov number, NCT00297895 .).

Published
2017

46. Truncating NFKB1variants cause combined NLRP3 inflammasome activation and type I interferon signaling and predispose to necrotizing fasciitis

Author

Nurmi, Katariina, Silventoinen, Kristiina, Keskitalo, Salla, Rajamäki, Kristiina, Kouri, Vesa-Petteri, Kinnunen, Matias, Jalil, Sami, Maldonado, Rocio, Wartiovaara, Kirmo, Nievas, Elma Inés, Denita-Juárez, Silvina Paola, Duncan, Christopher J.A., Kuismin, Outi, Saarela, Janna, Romo, Inka, Martelius, Timi, Parantainen, Jukka, Beklen, Arzu, Bilicka, Marcelina, Matikainen, Sampsa, Nordström, Dan C., Kaustio, Meri, Wartiovaara-Kautto, Ulla, Kilpivaara, Outi, Klein, Christoph, Hauck, Fabian, Jahkola, Tiina, Hautala, Timo, Varjosalo, Markku, Barreto, Goncalo, Seppänen, Mikko R.J., and Eklund, Kari K.

Abstract

In monogenic autoinflammatory diseases, mutations in genes regulating innate immune responses often lead to uncontrolled activation of inflammasome pathways or the type I interferon (IFN-I) response. We describe a mechanism of autoinflammation potentially predisposing patients to life-threatening necrotizing soft tissue inflammation. Six unrelated families are identified in which affected members present with necrotizing fasciitis or severe soft tissue inflammations. Exome sequencing reveals truncating monoallelic loss-of-function variants of nuclear factor κ light-chain enhancer of activated B cells(NFKB1) in affected patients.In patients’ macrophages and in NFKB1-variant-bearing THP-1 cells, activation increases both interleukin (IL)-1β secretion and IFN-I signaling. Truncation of NF-κB1 impairs autophagy, accompanied by the accumulation of reactive oxygen species and reduced degradation of inflammasome receptor nucleotide-binding oligomerization domain, leucine-rich repeat-containing protein 3 (NLRP3), and Toll/IL-1 receptor domain-containing adaptor protein inducing IFN-β (TRIF), thus leading to combined excessive inflammasome and IFN-I activity. Many of the patients respond to anti-inflammatory treatment, and targeting IL-1β and/or IFN-I signaling could represent a therapeutic approach for these patients.

Published
2024
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48. Health-related quality of life in different states of breast cancer - comparing different instruments.

Author

Rautalin, Mervi, Jahkola, Tiina, Färkkilä, Niilo, Sintonen, Harri, Saarto, Tiina, Taari, Kimmo, and Roine, Risto P.

Subjects
*BREAST tumor diagnosis, *BREAST tumor treatment, *BREAST tumors, *CANCER patients, *CANCER pain, *CONVALESCENCE, *FATIGUE (Physiology), *INSOMNIA, *METASTASIS, *MULTIVARIATE analysis, *SCIENTIFIC observation, *PALLIATIVE treatment, *QUALITY of life, *QUESTIONNAIRES, *REGRESSION analysis, *TUMOR classification, *DISEASE remission, *CROSS-sectional method, *RESEARCH methodology evaluation, *DISEASE progression, *SYMPTOMS, *CANCER & psychology, RESEARCH evaluation
Abstract

Background: The prognosis of breast cancer has improved significantly during the last few decades increasing the interest in health-related quality of life (HRQoL). The aim of this study was to compare the HRQoL scores produced by different instruments and to shed light on their validity in various states of breast cancer by studying the association of cancer-related symptoms with HRQoL. Material and methods: An observational, cross-sectional study of breast cancer patients treated in the Helsinki and Uusimaa Hospital District from September 2009 to April 2011. A total of 840 patients completed three HRQoL questionnaires: the EQ-5D-3L (including VAS), 15D and EORTC QLQ-30 and a questionnaire concerning sociodemographic factors. Patients were divided into five mutually exclusive groups: primary treatment (n=118), recovery (6-18 months from diagnosis) (n=150), remission (>18 months) (n=382), metastatic disease (n=176) and palliative care (n=14). The association of HRQoL with sociodemographic and clinical factors and cancer-related symptoms, screened by the EORTC QLQ- 30, was studied by multivariate modeling using stepwise linear regression analysis. Results: HRQoL scores were the best at the time closest to diagnosis and deteriorated with disease progression. The EQ-5D had a pronounced ceiling effect with 40.8% of the respondents scoring 1 (perfect health) compared to 6% for the 15D and 5.6% for VAS. In regression analyses, pain, fatigue and financial difficulties were the most important predictors of lower HRQoL. The 15D showed better discriminatory power and content validity. The EORTC QLQ-C30 functioning deteriorated in advanced states of the disease with physical, social and role functioning being the most affected. Insomnia, fatigue and pain were the most commonly reported symptoms in all groups. Conclusions: Different HRQoL instruments produce notably different HRQoL scores. The EQ-5D has a pronounced ceiling effect. Pain and fatigue are the most common symptoms associated with poor HRQoL in all disease states. [ABSTRACT FROM AUTHOR]

Published
2018
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49. Finnish translation, validation, and reproducibility of BREAST-Q modules relevant to breast cancer treatment

Author

Homsy, Pauliina, Repo, Jussi, Kuhlefelt, Charlotta, Lindford, Andrew, Ihalainen, Hanna, Kauhanen, Susanna, and Jahkola, Tiina

Abstract

Background and objective: Breast cancer and its treatments can have a marked impact on the patient health-related quality of life. The aim of this study was to produce and validate Finnish versions of the breast-conserving treatment, mastectomy and breast reconstruction modules of the BREAST-Q, a patient-reported outcome tool designed specifically for women undergoing treatment for breast cancer.Methods: The relevant BREAST-Q modules were translated to Finnish according to established guidelines. Altogether 777 preoperative women were recruited at the Breast Surgery Unit and the Plastic Surgery Unit of Helsinki University Hospital between December 2019 and March 2021. This included 541 patients scheduled for breast-conserving surgery, 86 for mastectomy, and 150 for breast reconstruction. Postoperative patients were recruited through a postal survey, approaching 500 women operated for breast cancer in 2017, including 250 women who had undergone breast-conserving surgery and 250 women who had undergone mastectomy, as well as 339 women who had undergone breast reconstruction between August 2017 and July 2019. The patients were invited to fill the BREAST-Q modules relevant to their treatment and the general health-related quality-of-life instrument SF-36. A repeat administration of the BREAST-Q was done 2 weeks later.Results: A total of 665 (41%) women participated in the study, 339 (44%) preoperatively and 326 (39%) postoperatively. The BREAST-Q subscales showed high internal consistency with most Cronbach’s alphas > 0.8. The repeatability of the subscales was excellent with most intra-class correlation coefficients > 0.75. Low or negligible correlation was observed between BREAST-Q subscales and SF-36 domains.Conclusions: The Finnish version of the BREAST-Q modules breast-conserving treatment, mastectomy, and breast reconstruction performs well in assessing the health-related quality of life of women undergoing surgery for breast cancer or breast reconstruction.

Published
2024
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