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Immunotherapy treatment with checkpoint inhibitors (ICIs) has led to a breakthrough in the treatment of oncological diseases. Despite its clinical effectiveness, this treatment differs from others, such as cytotoxic chemotherapy, in that it causes immune-related adverse events. This type of toxicity can affect any organ or organ system of the body. We present a literature review and a rare clinical case from our clinical practice, in which a patient with metastatic clear cell renal carcinoma was treated with a single dose of dual checkpoint blockade (cytotoxic T-lymphocyte-4 (CTLA-4) and programmed death-1 (PD-1)) and simultaneously diagnosed with colitis, hepatitis, and nephritis. After early immunosuppressive treatment with the glucocorticoids, complete organ function recovery was achieved. The follow-up revealed a sustained complete response lasting more than a year.

Abstract Background Pulmonary tumour thrombotic microangiopathy (PTTM) is a fatal disease in which tumour cells embolize to the pulmonary vasculature leading to pulmonary hypertension and right heart failure. Early diagnosis is essential for timely treatment which can reduce intimal pulmonary vascular proliferation and prolong survival, improve the symptoms. Due to rare occurrences and no clear diagnostic guidelines the disorder usually is found post-mortem. We present a review of this rare disease and a case of post-mortem diagnosed pulmonary tumour thrombotic microangiopathy in a young female. Case presentation 51 years old woman presented with progressively worsening dyspnea, right ventricular failure signs and symptoms. Computerized tomography denied pulmonary embolism. 2D transthoracic echocardiography demonstrated right ventricle dilatation and dysfunction, severely increased systolic pulmonary pressure. Right heart catheterization revealed pre-capillary pulmonary hypertension with mean pulmonary artery pressure of 78 mmHg, pulmonary wedge pressure of 15 mmHg, reduced cardiac output to 1.78 L/min with a calculated pulmonary vascular resistance of 35 Wood units, and extremely low oxygen saturation (26%) in pulmonary artery. Because of worsening ascites, pelvic magnetic resonance imaging was performed, tumours in both ovaries were diagnosed. Due to the high operative risk, detailed tumour diagnosis surgically was not established. The patient developed progressive cardiorespiratory failure, unresponsive to optimal heart failure drug treatment. A postmortem morphology analyses revealed tumorous masses in pre-capillary lung vessels, right ventricle hypertrophy, ovary adenocarcinoma. Conclusions An early diagnosis of PTTM is essential. Most cases are lethal due to respiratory failure progressing rapidly. Patients with a history of malignancy, symptoms and signs implying of PH should be considered of having PTTM. If detected early enough, combination of chemotherapy with specific PH therapy is believed to be beneficial in reducing intimal proliferation and prolonging survival, along with improving the symptoms.

Ampulla of Vater metastases from renal cell carcinoma are rare. The time between detection of the primary tumour and its metastasis may extend to years. Management should be aggressive, since the prognosis of renal cell carcinoma is unpredictable and curative surgery of metastases may extend patient survival and even lead to definite cure. Herein we report a case of long-term survival after successful surgical treatment of a renal cell carcinoma metastasis to the ampulla of Vater. A 62-year-old man with a history of renal cell carcinoma in the left kidney underwent a successful left nephrectomy. Eight months later duodenoscopy showed a tumour at the site of papilla of Vater. Biopsy confirmed the diagnosis of carcinoma. Contrast enhanced computer tomography scan verified the periampullary mass, dilatation of the pancreatic and the common bile duct. No radiological signs of either local advancement or distant metastases were present. Pylorus-preserving pancreatoduodenectomy with lymphadenectomy was performed. Pathology report disclosed metastatic lesions in the papilla of Vater from the clear cell carcinoma of the kidney. The postoperative course was uneventful, and the patient lived for 14 years after pancreatoduodenectomy and, following thorough investigations, was free from local and systemic recurrence. Pancreatoduodenectomy can provide long-term survival in selected cases with solitary papilla of Vater metastasis from renal cell carcinoma. Favourable long-term survival rates suggest that these patients should be considered candidates for pancreatoduodenectomy if experienced pancreatic surgeon is available and no other metastases are found.

Abstract Background Non-small cell lung cancer (NSCLC) remains the most common cause of cancer related death worldwide. Tumor-infiltrating macrophages are believed to play an important role in growth, progression, and metastasis of tumors. In NSCLC, the role of macrophages remains controversial; therefore, we aimed to evaluate the distribution of macrophages (M1 and M2) in tumor islets and stroma and to analyze their relations to patients’ survival. Methods Lung tissue specimens from 80 NSCLC patients who underwent surgical resection for NSCLC (pathological stage I-III) and 16 control group subjects who underwent surgery because of recurrent spontaneous pneumothorax were analyzed. Immunohistochemical double staining of CD68/iNOS (markers for M1 macrophages) and CD68/CD163 (markers for M2 macrophages) was performed and evaluated in a blinded manner. The numbers of M1 and M2 macrophages in tumor islets and stroma were counted manually. Results Predominant infiltration of M1 and M2 macrophages was observed in the tumor stroma compared with the tumor islets. M2 macrophages predominated over M1 macrophages in the tumor tissue. Tumor islets-infiltrating M1 macrophages and the number of total tumor-infiltrating M2 macrophages were independent predictors of patients survival: high infiltration of M1 macrophages in tumor islets was associated with increased overall survival in NSCLC (P

Background and objective: The immune system plays an important role in non-small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate the infiltration patterns of CD4+ and CD8+ T cells in NSCLC and to analyze their relation to COPD, smoking status and other clinicopathologic variables. Materials and methods: Lung tissue specimens from 50 patients who underwent surgery for NSCLC (stages I–III) and 10 control group subjects were analyzed immunohistochemically. Results: NSCLC patients had a greater number of CD4+ and CD8+ T cells infiltrating the lung tissue than the control group (P = 0.001) with predominant infiltration in the tumor stroma. We found a significant association between the number of total and tumor stroma-infiltrating CD4+ and CD8+ T cells, and smoking status (P

Tobacco smoking is inconsistently associated with breast cancer. Although some studies suggest that breast cancer risk is related to passive smoking, little is known about the association with breast cancer by tumor hormone receptor status. We aimed to explore the association between lifetime passive smoking and risk of breast cancer subtypes defined by estrogen receptor and progesterone receptor status among non-smoking Caucasian women. A hospital-based case-control study was performed in 585 cases and 1170 controls aged 28-90 years. Information on lifetime passive smoking and other factors was collected via a self-administered questionnaire. Logistic regression was used for analyses restricted to the 449 cases and 930 controls who had never smoked actively. All statistical tests were two-sided. Adjusted odds ratio of breast cancer was 1.01 (95% confidence interval (CI): 0.72-1.41) in women who experienced exposure to passive smoking at work, 1.88 (95% CI: 1.38-2.55) in women who had exposure at home, and 2.80 (95% CI: 1.84-4.25) in women who were exposed at home and at work, all compared with never exposed regularly. Increased risk was associated with longer exposure: women exposed ≤ 20 years and > 20 years had 1.27 (95% CI: 0.97-1.66) and 2.64 (95% CI: 1.87-3.74) times higher risk of breast cancer compared with never exposed (Ptrend < 0.001). The association of passive smoking with hormone receptor-positive breast cancer did not differ from that with hormone receptor-negative breast cancer (Pheterogeneity > 0.05). There was evidence of interaction between passive smoking intensity and menopausal status in both overall group (P = 0.02) and hormone receptor-positive breast cancer group (P < 0.05). In Caucasian women, lifetime exposure to passive smoking is associated with the risk of breast cancer independent of tumor hormone receptor status with the strongest association in postmenopausal women.

Alcohol is a well-established risk factor for breast cancer, but pathways involved in alcohol-related breast carcinogenesis are not clearly defined. We examined the association between low-to-moderate alcohol intake and breast cancer subtypes by tumor hormone receptor status.A hospital-based case-control study was performed in 585 cases and 1,170 controls. Information on alcohol intake and other risk factors was collected via a questionnaire. Logistic regression was used for analyses. All statistical tests were two-sided.The odds ratio of breast cancer was 1.75 (95% confidence interval [CI]: 1.21-2.53) in women who consumed ≤5 drinks/week, and 3.13 (95% CI: 1.81-5.43) in women who consumed >5 drinks/week, both compared with non-drinkers for ≥10 years, after adjustment for age and other confounders. The association of alcohol intake with estrogen receptor-positive breast cancer was stronger than with estrogen receptor-negative: the odds ratio per 1 category increase was 2.05 (95% CI: 1.49-2.82) and 1.29 (95% CI: 0.85-1.94) (P-heterogeneity = 0.07). There was no evidence of an interaction between alcohol intake and menopausal status (P = 0.19) in overall group; however, it was significant in estrogen receptor-positive breast cancer (P = 0.04).Low-to-moderate alcohol intake is associated with the risk of estrogen receptor-positive breast cancer with the strongest association in postmenopausal women. Since alcohol intake is a modifiable risk factor of breast cancer, every woman should be informed and advised to control alcohol use.

Rimtautas Gudas1, Romas Jonas Kalesinskas1, Giedrius Bernotavičius1, Eglė Monastyreckienė2, Angelija Valančiūtė3, Darius Pranys4 1 Kauno medicinos universiteto klinikų Ortopedijos ir traumatologijos klinika Eivenių g. 2, LT-50009 Kaunas el paštas: rimtautas@kmu.lt 2 Kauno medicinos universiteto klinikų Radiologijos klinika 3 Kauno medicinos universiteto Embriologijos ir histologijos katedra 4 Kauno medicinos universiteto Patologinės anatomijos klinika Tikslas Mūsų prospektyvaus klinikinio tyrimo tikslas – įvertinti mozaikinės autologinės transplantacijos rezultatus gydant kelio sąnario kremzlės pažeidimus. Ligoniai ir metodai 1998–2002 metais KMU Ortopedijos ir traumatologijos klinikoje atliktos 87 autologinės mozaikinės transplantacijos operacijos esant kelio sąnario kremzlės ir kaulo pažeidimams. Pacientų amžiaus vidurkis operacijų metu buvo 24,74 ± 7,20 metų (14–40 metų). Simptomai vidutiniškai truko 21,32 ± 5,57 mėnesio, o pacientai įvertinti praėjus vidutiniškai 24,4 mėnesio (nuo 12 iki 60 mėnesių) po operacijos. Rezultatai apibendrinti naudojant ICRS (International Cartilage Repair Society) anketą, 13 (15%) atvejų – remiantis kartotinių artroskopijų metu atliktu makroskopiniu įvertinimu, 9 (11%) atvejais – histologiniu tyrimu, 57 (67%) atvejais – BMR ir visais atvejais – rentgeno tyrimais. Visus anketinius įvertinimus atliko nepriklausomas gydytojas ortopedas prieš operacijas ir po operacijų praėjus dvylikai, dvidešimt keturiems, trisdešimt šešiems, keturiasdešimt aštuoniems ir šešiasdešimčiai mėnesių. Nepriklausomi nuo tyrimo gydytojai, radiologas ir patologas, atliko visus BMR ir histomorfologinius įvertinimus. Rezultatai Praėjus vidutiniškai 24,4 mėnesio po mozaikinės transplantacijos, ICRS anketos būdu nustatytas klinikinis rezultatų pagerėjimas (p < 0,05). Funkcinis ir objektyvus įvertinimas pagal ICRS anketą buvo toks: 93% atvejų gauti geri ir labai geri operacinio gydymo rezultatai, kitais atvejais (7%) gydymo rezultatai buvo patenkinami. Kartotinių artroskopijų metu (remiantis ICRS protokolu), po operacijų praėjus vidutiniškai 12,4 mėnesio, 11 (84%) iš 13 atvejų buvo nustatytas geras ir labai geras sąnario kremzlės makroskopinis atsitaisymas. Sąnario kremzlės biopsijos ir histologinis tyrimas buvo atliktas 11% pacientų, ir daugumos jų (remiantis ICRS protokolu) sąnario kremzlės ir pokremzlinio kaulo atitaisymo koeficientas buvo geras. BMR tyrimas parodė, kad 94% pacientų sąnario paviršius atkurtas gerai arba labai gerai. Išvados Mūsų tyrimas parodė, kad po mozaikinės autologinės transplantacijos praėjus vidutiniškai 24,4 mėnesio (nuo 12 iki 60 mėn.) fiziškai aktyvių pacientų, kuriems buvo pažeista kelio sąnario kremzlė, klinikinė ir funkcinė būklė labai pagerėjo. Dauguma pacientų po kremzlės mozaikinės autologinės transplantacijos atgauna prieš pažeidimą buvusį fizinio aktyvumo lygį. Histomorfologinis persodintų transplantatų tyrimas parodė, kad visais tirtais atvejais išsilaikė hialininės kremzlės struktūra ir fibroelastinio audinio intarpai tarp transplantatų. Reikšminiai žodžiai: sąnario kremzlės pažeidimai, mozaikinė transplantacija Mosaic-like autologous osteochondral transplantation for the treatment of knee joint articular cartilage injuries Rimtautas Gudas1, Romas Jonas Kalesinskas1, Giedrius Bernotavičius1, Eglė Monastyreckienė2, Angelija Valančiūtė3, Darius Pranys4 Objective The purpose of this prospective clinical study was to evaluate the outcomes of mosaic type autologous osteochondral transplantation procedure for the treatment of the articular cartilage defects of the knee joint. Patients and methods Between 1998 and 2002, a total of 85 patients underwent an osteochondral autologous transplantation (mosaicplasty) procedure for osteochondral or chondral knee joint injury. The patients were evaluated using the ICRS score, arthroscopically, histologically, with MRI and X-ray examinations. The mean duration of symptoms was 21.32 ± 5.57 months and the mean follow-up was 24.4 months (range, 12 to 60 months). The mean age of the patients during the surgery was 24.74 ± 7.20 years (range, 14 to 40 years). An independent observer performed a follow-up examination after six, twelve, twenty-four, thirty-six and forty-eight months. In 13 (15%) of 85 cases 12.4 months postoperatively, arthroscopy with biopsy for histological evaluation was carried out. A radiologist and a pathologist, both blinded to each patient’s treatment, did the radiological and histological evaluations. Results After 24.4 months all the patients showed a significant clinical improvement (p < 0.05). The cartilage Repair Society (ICRS) score, functional and objective assessment revealed 93% to have excellent or good results after mosaicplasty; 7% were fair 24.4 months (range, 12–60 months) after the operations. The ICRS evaluation showed a significant improvement after the mosaicplasty procedure 24.4 months following operations (p = 0.005). No serious complications were reported. The ICRS for macroscopic evaluation during arthroscopy 12.4 months after mosaicplasty demonstrated excellent or good repair in 11 (84%) of 13 cases. Biopsy specimens were obtained from 9 (69%) of 13 patients, and histological evaluation of repair showed good scores (according to ICRS) for most samples after mosaicplasty. A MRI evaluation demonstrated excellent or good repairs in 94% after mosaicplasty. Conclusions On an average after 24.4 months (range, 12 to 60 months) of follow-up, our clinical study has shown a significant improvement of the clinical status of the physically active patients after the mosaic type autologous osteochondral transplantation for the repair of articular cartilage defects in the knee. Histologically, the osteochondral cylinder transplants retained hyaline cartilage. Keywords: articular cartilage injury, osteochondral mosaic-like transplantation

Abstract Background/Purpose  The majority of surgeons agree that ampullary adenocarcinoma should be removed by partial pancreatoduodenectomy. Favoring extended resection, based on the uncertainty of the preoperative diagnosis and the higher probability of clear resection margins, we aimed to disclose the results of this surgical procedure in terms of postoperative morbidity and mortality, and to identify prognosticators of long-term survival. Methods  We documented, prospectively, 25 consecutive patients with adenocarcinoma of the papilla of Vater in whom pylorus-preserving pancreatoduodenectomy was performed. Clinical data, pathology reports, International Union Against Cancer (UICC) tumor stage, postoperative morbidity, mortality, and long-term follow-up results were evaluated. The Kaplan-Meier method and log-rank test were applied for univariate analysis. The Cox proportional hazard model was used for multivariate analysis. Results  Postoperative mortality was 4%, overall morbidity was 32%, and pancreas-associated morbidity was 8%. Mean survival time was 53.8 months. Tumor size, N status, UICC stage, lymphatic invasion, blood vessel infiltration, R0 resection, and age of patient at the cutoff of 70 years were independent predictors of survival on univariate analysis. Multivariate analysis, however, disclosed no independent predictors of prognosis. Conclusions  Pancreatoduodenectomy for ampullary carcinoma is reasonable in terms of postoperative morbidity and mortality. Tumor-related factors, R0 resection, and advanced age appeared as the main predictors of survival. [ABSTRACT FROM AUTHOR]