71 research outputs found

    Diagnosis and Treatment of Pseudomyxoma Peritonei

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    Abstract Pseudomyxoma peritonei (PMP) is best treated by surgery. It was formerly treated by serial debulking. The current gold standard is complete cytoreductive surgery (CRS) to be followed by hyperthermic intraperitoneal chemotherapy (HIPEC). Improved survival figures for patients treated by CRS and HIPEC combined have been reported recently. The aim of this PhD research was to evaluate (I) the outcome of patients treated by serial debulking in Helsinki University Central Hospital, (II) investigate the clinical manifestation of the disease, (III) assess the feasibility of CRS and HIPEC modality in combination, and (IV) compare results of serial debulking and CRS with HIPEC in patients with PMP. The surgical data and the survival outcome of 33 patients that were treated by serial debulking were analyzed in study I. The symptoms and signs of 82 patients with PMP were investigated in study II. Study III included 90 patients, who were evaluated in our facility and then given HIPEC when practicable. The characteristics that were associated with technically successful administration of HIPEC were analysed. The outcome of 87 patients treated in the HIPEC era was compared with those treated before the HIPEC era in study IV. The 5-year and 10-year overall survival (OS) rates were 67% and 31%. Four patients (12%) presented with no apparent evidence of disease at the completion of follow-up (I). The most common symptom of PMP was abdominal pain in 23% of the cases (II). Of 53 women, 26 (49%) underwent their initial operations because of presumed ovarian tumour. Of 29 men, 13 (45%) underwent their initial operations with a suspicion of PMP. Of the 90 patients assessed, 56 (62%) were feasible for HIPEC (III). Low-grade tumour (P=0.013), age under 65 (P=0.004), and serum CEA under 5.0µg/L (P=0.003) were associated with successful administration of HIPEC. The 5-year OS rates were 69% for the HIPEC era and 67% for the debulking era (IV). The proportion of patients who presented with no evidence of disease was higher for the HIPEC-era group than for the debulking-era group (54% vs. 24%). Patients who were treated by CRS and HIPEC combined managed well, but it is unfeasible to deliver HIPEC to every patient. A comparison of the 5-year OS rates of HIPEC era with those of the debulking era showed them to be approximately equal, when the whole patient population was included for the comparison. The natural progression of PMP is slow and thus the survival difference may only become apparent in follow-up periods in excess of 5-years. The proportion of patients who had undergone curative treatment may be higher in the HIPEC era.Uusi hoitokäytäntö on mullistanut vatsaontelon limakasvaimen hoidon Vatsakalvon pseudomyksooma on hyvin harvinainen kasvaintauti. Aiemmin tautia on hoidettu toistetuilla leikkauksilla, mutta nykyään pyritään poistamaan kasvain yhdellä leikkauksella äärimmäisen tarkasti. Onnistuneen poiston jälkeen potilaille annetaan solunsalpaajahoito jo leikkauksen aikana. Väitöstutkimukseni mukaan hoidon onnistuessa yhdeksän kymmenestä leikkauspotilaasta on elossa viiden vuoden kuluttua. Tauti saa alkunsa lähes poikkeuksetta umpilisäkkeen limakalvon soluista, jotka leviävät umpilisäkkeen ulkopuolelle vatsaontelon pintaa pitkin. Kasvainsolut jatkavat lisääntymistä ja limantuotantoa vatsaontelossa ja leviävät vähitellen eri sisäelinten pinnoille. Taudin edetessä koko vatsaontelo täyttyy limansekaisesta kasvainmateriaalista, ja vatsaa pullistuu jo näkyvästi ulospäin. Ilman hoitoa sisäelinten toiminta häiriintyy kasvainmassan vaikutuksesta. Lopulta tauti johtaa kuolemaan. Tautia on perinteisesti hoidettu toistuvilla leikkauksilla. Usein kasvainmassaa on kuitenkin jäänyt vatsaonteloon ja jonkin ajan kuluttua uusi leikkaus on jälleen ollut edessä. Lopulta leikkaushoito ei enää ole ollut mahdollista tai turvallista. Taudin hitaan etenemisen takia perinteisilläkin leikkauksilla hoidettujen potilaiden lyhytaikainen ennuste on kohtalaisen hyvä. Uusi hoitokäytäntö on mullistanut pseudomyksooman hoidon. Nykyään pyritään erittäin tarkkaan leikkaukseen, jossa kaikki kasvainkudos pyritään poistamaan jo ensimmäisellä yrityksellä. Tarvittaessa elinpoistoja tehdään runsaasti. Merkittävimpänä uutena asiana poistetaan koko vatsakalvo, joka verhoaa normaalisti vatsaontelon seinämää. Jos koko vatsaontelo saadaan puhdistettua kasvainmassasta, lämmitetty solunsalpaajaliuos annostellaan leikkauksen aikana vatsaonteloon (HIPEC, Hyperthermic Intraperitoneal Chemotherapy). Vaikka uusi hoitokäytäntö on otettu laajalti käyttöön pseudomyksooman hoidossa maailmalla, se ei sovellu käytettäväksi kaikille potilaille. Täydelliseen kasvainmassan poistoon pyrkivä leikkaus on erittäin raskas kirurginen toimenpide. Leikkaukseen liittyy korkea komplikaatio- ja kuolleisuusriski. Potilaan muut sairaudet voivat estää toimenpiteen turvallisen suorittamisen. Esimerkiksi vakavat sydän- ja keuhkosairaudet voivat olla esteitä. Uusi hoito on kallis yhteiskunnalle ja kuluttaa terveydenhuollon voimavaroja. Vertaan väitöskirjassani hoidon tuloksia uuden ja vanhan hoidon aikakaudella ja arvioin, kenelle uusi hoito ylipäätään sopii. Lyhytaikaisen seurannan jälkeen uuden ja vanhan hoidon tuloksissa ei ole eroa, kun kaikki tautiin sairastuneet otetaan mukaan vertailuun. Viiden vuoden seurannan jälkeen 67 prosenttia vanhan hoidon aikakaudella hoidetuista on elossa. Vastaavasti 69 prosenttia uuden hoitomuodon aikakaudella hoidetuista on elossa. Löydös selittyy etenkin sillä, että hoitoa ei voida antaa kaikille pseudomyksoomaan sairastuneille. Väitöskirjatutkimuksen potilaista 62 prosenttia soveltuu HIPEC-hoitoon ja loput on hoidettu perinteisellä tavalla. Kuitenkin sellaisista potilaista, joille on annettu uusi hoitomuoto, 93 prosenttia on elossa viiden vuoden seurannan jälkeen. Lisäksi sellaisten potilaiden osuus, joilla ei seurannan jälkeen havaita tautia uuden hoidon aikakaudella, on suurempi (54 %) kuin vanhan hoidon aikakaudella (24 %). Tutkimuksen perusteella voidaan todeta, että potilaat hyötyvät uudesta hoidosta. Kaikille se ei valitettavasti sovi. Heitä hoidetaan edelleen perinteisellä tavalla. Vasta pidempi seuranta-aika osoittaa uuden hoidon lopullisen tehon

    Active surveillance versus initial surgery in the long-term management of Bosniak IIF-IV cystic renal masses

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    There may be surgical overtreatment of complex cystic renal masses (CRM). Growing evidence supports active surveillance (AS) for the management for Bosniak IIF-III CRMs. We aimed to evaluate and compare oncological and pathological outcomes of Bosniak IIF-IV CRMs treated by initial surgery (IS) or AS. We identified retrospectively 532 patients with CRM counseled during 2006-2017. IS and AS were delivered to, respectively, 1 and 286 patients in Bosniak IIF, to 54 and 85 patients in III and to 85 and 21 patients in Bosniak IV. Median follow-up was 66 months (IQR 50-96). Metastatic progression occurred for 1 (0.3%) AS patient in Bosniak IIF, 1 IS (1.8%) and 1 AS (1.2%) patient in Bosniak III and 5 IS (3.5%) patients in Bosniak IV, respectively. Overall 5-year metastasis-free survival was 98.9% and cancer-specific survival was 99.6% without statistically significant difference between IS and AS in Bosniak IIF-IV categories. AS did not increase the risk of metastatic spread or cancer-specific mortality in patients with Bosniak IIF-IV. Our data indicate AS in Bosniak IIF and III is safe. Surgery is the primary treatment for Bosniak IV due to its high malignancy rate.Peer reviewe

    Serum tumour associated trypsin inhibitor, as a biomarker for survival in renal cell carcinoma : Scandinavian Journal of Urology

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    Abstract Objective Tumour associated trypsin inhibitor (TATI) is a peptide that is a marker for several tumours. TATI may also behave as an acute phase reactant in severe inflammatory disease. Overexpression of TATI predicts an unfavourable outcome for many cancers. This study aimed to evaluate the prognostic value of pre- and postoperative concentration of TATI in serum (S-TATI) of patients with renal cell carcinoma (RCC). Materials and methods S-TATI was determined by time resolved immunofluorometric assay in preoperative and postoperative samples that were collected from 132 RCC patients, who underwent partial or complete nephrectomy in Helsinki University Hospital from May 2005 to July 2010. Results Preoperative S-TATI was significantly associated with tumour stage, lymph-node involvement, metastatic stage, Chronic Kidney Disease Stage (CKD grade), and preoperative C-reactive protein level (p?Peer reviewe

    Multiple components of PKA and TGF-beta pathways are mutated in pseudomyxoma peritonei

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    Pseudomyxoma peritonei (PMP) is a subtype of mucinous adenocarcinoma mainly restricted to the peritoneal cavity and most commonly originating from the appendix. The genetic background of PMP is poorly understood and no targeted treatments are currently available for this fatal disease. While RAS signaling pathway is affected in most if not all PMP cases and over half of them also have a mutation in the GNAS gene, other genetic alterations and affected pathways are, to a large degree, poorly known. In this study, we sequenced whole coding genome of nine PMP tumors and paired normal tissues in order to identify additional, commonly mutated genes and signaling pathways affected in PMP. These exome sequencing results were validated with an ultra-deep amplicon sequencing method, leading to 14 validated variants. The validated results contain seven genes that contribute to the protein kinase A (PKA) pathway. PKA pathway, which also contains GNAS, is a major player of overproduction of mucin, which is the characteristic feature of PMP. In addition to PKA pathway, we identified mutations in six genes that belong to the transforming growth factor beta (TGF-beta) pathway, which is a key regulator of cell proliferation. Since either GNAS mutation or an alternative mutation in the PKA pathway was identified in 8/9 patients, inhibition of the PKA pathway might reduce mucin production in most of the PMP patients and potentially suppress disease progression.Peer reviewe

    Risk of Complications After Hydrocele Surgery : A Retrospective Multicenter Study in Helsinki Metropolitan Area

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    Publisher Copyright: © 2022 The AuthorsBackground: Despite being one of the most frequent urological procedures, the risk estimates for complications after hydrocele surgery (hydrocelectomy) are uncertain. Decision-making about hydrocelectomy involves balancing the risk of complications with efficacy of surgery—a tradeoff that critically depends on the complication risks of hydrocele surgery. Objective: To examine the 90-d risks of complications of hydrocele surgery in a large, contemporary sample. Design, setting, and participants: We retrospectively reviewed all surgeries performed for nonrecurrent hydroceles conducted in all five Helsinki metropolitan area public hospitals from the beginning of 2010 till the end of 2018, and evaluated the complication outcomes. Outcome measurements and statistical analysis: The following outcomes were evaluated: (1) risk of moderate or severe (Clavien-Dindo II–V) hydrocele surgery complications, (2) risk of reoperation due to a surgical complication, and (3) risk of an unplanned postoperative visit to the emergency room or outpatient clinic, all within 90 d after surgery. Results and limitations: We identified 866 hydrocele operations (38 [4.3%] bilateral operations). A total of 139 (16.1%) patients had moderate or severe hydrocele surgery complications within 90 d after surgery. Of the 139 complications, 94 were (10.9% of all or 67.6% of patients with moderate or severe complications) Clavien-Dindo grade II, 43 (5.0% and 30.9%, respectively) grade III, two (0.2% and 1.4%, respectively) grade IV, and none grade V. A total of 45 patients (5.2% of all and 32.4% of those who had moderate or severe complications) required immediate reoperation due to complications. All together 219 operated patients (25.3% of all operated patients) had an unplanned visit to the emergency room. The retrospective study design limits the reliability of the results. Conclusions: Complications after hydrocele surgery are common and warrant further research. These estimates can be useful in shared decision-making between clinicians and patients. Patient summary: We investigated the complication rates after hydrocele surgery and found that complications are common after a procedure often considered minor: every ninth patient had a moderate and every 20th a severe complication. Every fourth patient had an unplanned postoperative visit to the emergency room.Peer reviewe

    The tumor and plasma cytokine profiles of renal cell carcinoma patients

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    Renal cell carcinoma (RCC) accounts for 90% of all renal cancers and is considered highly immunogenic. Although many studies have reported the circulating peripheral cytokine profiles, the signatures between the tumor tissue and matching healthy adjacent renal tissue counterparts have not been explored. We aimed to comprehensively investigate the cytokine landscape of RCC tumors and its correlation between the amount and phenotype of the tumor infiltrating lymphocytes (TILs). We analyzed the secretion of 42 cytokines from the tumor (n = 46), adjacent healthy kidney tissues (n = 23) and matching plasma samples (n = 33) with a Luminex-based assay. We further explored the differences between the tissue types, as well as correlated the findings with clinical data and detailed immunophenotyping of the TILs. Using an unsupervised clustering approach, we observed distinct differences in the cytokine profiles between the tumor and adjacent renal tissue samples. The tumor samples clustered into three distinct profiles based on the cytokine expressions: high (52.2% of the tumors), intermediate (26.1%), and low (21.7%). Most of the tumor cytokines positively correlated with each other, except for IL-8 that showed no correlation with any of the measured cytokine expressions. Furthermore, the quantity of lymphocytes in the tumor samples analyzed with flow cytometry positively correlated with the chemokine-family of cytokines, CXCL10 (IP-10) and CXCL9 (MIG). No significant correlations were found between the tumor and matching plasma cytokines, suggesting that circulating cytokines poorly mirror the tumor cytokine environment. Our study highlights distinct cytokine profiles in the RCC tumor microenvironment and provides insights to potential biomarkers for the treatment of RCC.Peer reviewe

    T and NK cell abundance defines two distinct subgroups of renal cell carcinoma

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    Renal cell carcinoma (RCC) is considered as an immunogenic cancer. Because not all patients respond to current immunotherapies, we aimed to investigate the immunological heterogeneity of RCC tumors. We analyzedthe immunophenotype of the circulating, tumor, and matching adjacent healthy kidney immune cells from 52 nephrectomy patients with multi-parameter flow cytometry. Additionally, we studied the transcriptomic and mutation profiles of 20 clear cell RCC (ccRCC) tumors with bulk RNA sequencing and a customized pan-cancer gene panel. The tumor samples clustered into two distinct subgroups defined by the abundance of intratumoral CD3+ T cells (CD3(high), 25/52) and NK cells (NKhigh, 27/52). CD3(high) tumors had an overall higher frequency of tumor infiltrating lymphocytes and PD-1 expression on the CD8+ T cells compared to NKhigh tumors. The tumor infiltrating T and NK cells had significantly elevated expression levels of LAG-3, PD-1, and HLA-DR compared to the circulating immune cells. Transcriptomic analysis revealed increased immune signaling (IFN-gamma, TNF-alpha via NF-kappa B, and T cell receptor signaling) and kidney metabolism pathways in the CD3(high) subgroup. Genomic analysis confirmed the typical ccRCC mutation profile including VHL, PBRM1, and SETD2 mutations, and revealed PBRM1 as a uniquely mutated gene in the CD3(high) subgroup. Approximately half of the RCC tumors have a high infiltration of NK cells associated with a lower number of tumor infiltrating lymphocytes, lower PD-1 expression, a distinct transcriptomic and mutation profile, providing insights to the immunological heterogeneity of RCC which may impact treatment responses to immunological therapies.Peer reviewe

    Use of venous-thrombotic-embolic prophylaxis in patients undergoing surgery for renal tumors: a questionnaire survey in the Nordic countries (The NORENCA-2 study)

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    Purpose: To examine the variation in venous thromboembolism prophylactic treatment (VTEP) among renal cancer patients undergoing surgery. Materials and methods: An Internet-based questionnaire on renal tumor management before and after surgery was mailed to all Nordic departments of urology. The questions focused on the use of VTEP and were subdivided into different surgical modalities. Results: Questionnaires were mailed to 91 institutions (response rate 53%). None of the centers used VTEP before surgery, unless the patient had a vena caval tumor thrombus. Overall, the VTEP utilized during hospitalization for patients undergoing renal surgery included early mobilization (45%), compression stockings (52%) and low-molecular-weight heparin (89%). In patients undergoing open radical Nx, 80% of institutions used VTEP during their hospitalization (23% compression stockings and 94% low-molecular-weight heparin). After leaving the hospital, the proportion and type of VTEP received varied considerably across institutions. The most common interval, used in 60% of the institutions, was for a period of 4 weeks. The restriction to the Nordic countries was a limitation and, therefore, may not reflect the practice patterns elsewhere. It is a survey study and, therefore, cannot measure the behaviors of those institutions that did not participate. Conclusion: We found variation in the type and duration of VTEP use for each type of local intervention for renal cancer. These widely disparate variations in care strongly argue for the establishment of national and international guidelines regarding VTEP in renal surgery.Peer reviewe
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