Autoimmune Encephalitis following Checkpoint Inhibitor Therapy in a Patient with Metastatic Melanoma in Complete Remission.

The use of immune checkpoint inhibitors (ICIs) in cancer is increasing. Their side effects are mainly due to the triggering of autoimmunity, which are mild or moderate and include skin rash, colitis, hepatitis, endocrine disorders, myositis, interstitial lung disorder, etc., in most cases during the course of therapy. Autoimmune encephalitis (AE) is rare in cancer patients treated with ICIs. Fifty patients with ICI-related encephalitis were identified in a recent review. Herein, we report a case of pembrolizumab associated with AE with a favorable short-term prognosis. A 68-year-old man with malignant metastatic melanoma achieved complete remission after pembrolizumab treatment. However, 10 months after pembrolizumab cessation due to grade 3 diarrhea, he developed confusion, an altered mental status, progressive memory loss, and gait disturbance. He was admitted to the neurologic department, and a comprehensive neurological workup, brain magnetic resonance imaging, cerebral fluid analysis, EEG, and blood test allowed the diagnosis of autoimmune encephalitis. The patient was treated with plasmapheresis, a high dose of intravenous steroids, and intravenous immunoglobulins. The patient improved, and he is now well with a performance status of 1. This case is interesting since the AE developed approximately 10 months after the cessation of immunotherapy, the underlying cancer was in complete remission, and the AE showed a good response after the treatment was performed.

[Territorial-based management of patients with cancer on active treatment following the Piacenza (north Italy) Model. Results of 4 consecutive years.] / Le cure oncologiche ed ematologiche sul territorio secondo il modello dell'ASL di Piacenza. Rendiconto di 4 anni consecutivi.

INTRODUCTION: The natural history of cancer has radically changed in the last decade. The burden of travel from patient's residence to health care providers is an important issue that can influence access to diagnosis and treatment of cancer; however this issue is quite neglect by the medical community and by the national health system. In addition, community care in the oncology field is actually debated. METHODS: In the district of Piacenza an innovative model to deliver onco-hematologic treatment near the residence of patients was initiated some years ago. The oncologic and hematologic treatments are delivered by specialized nurses under supervision of medical oncologists or hematologists at the 3 community hospital and at 1 house of health in the district of Piacenza. We conducted a retrospective study involving 1,339 cancer patients (CPs) managed and treated near their residence, CPs were on active medical treatment at the oncology and hematology department Azienda sanitaria (ASL) of Piacenza (North Italy). The electronic data base of the antiblastic drug unit (UFA) of the ASL Piacenza, provided: the number of patients treated each year, number of treatments and the accesses to the territorial medical structure each year. The kms saved to reach the nearest territorial structures instead of the oncologic unit of the city hospital, were registered and recorded. RESULTS: During a 4 years period, from January 2017 to December 2020, 1,339 CPs were treated near their residence, 278 in the year 2017, 347 in 2018, 354 in 2019 and 360 in 2020. The total accesses for treatment in 4 years were 10,003: 2,214 in the year 2017, 2,652 in 2018, 2,524 in 2019 and 2,613 in 2020. The mean distance saved for each patient was 937 kms in the year 2017, 891 in 2018, 879 in 2019, 920 in 2020, totally a mean of 3,627 kms in the 4 years. DISCUSSION AND CONCLUSION: We believe that the results of our retrospective study highlight the possibility of treating cancer patients in territorial structures near their residence, with advantages for patients themselves, their caregivers and for the entire community.

Life Threatening, Allopurinol-related Dress Syndrome as a Rare Cause of Fever of Unknown Origin.

Drug reaction eosinophilia with systemic symptoms (DRESS) syndrome is a potentially life threatening condition secondary to the usage of a wide type of drugs. A 38-year-old woman under allopurinol therapy for hyperuricemia was admitted in our department with fever and a diffuse cutaneous erythematous eruption. A few days after admission she developed rapidly progressive signs of acute liver and kidney failure. Subsequently, her clinical conditions shortly improved. The histologic findings obtained from skin and liver biopsies were consistent with a toxic drug reaction. The patient completely recovered and has been healthy for five years.

Ultrasound guidance reduces pneumothorax rate and improves safety of thoracentesis in malignant pleural effusion: report on 445 consecutive patients with advanced cancer.

BACKGROUND: Malignant pleural effusion (MPE) is an extremely common problem affecting cancer patients, and thoracentesis is an essential procedure in an attempt to delineate the etiology of the fluid collections and to relieve symptoms in affected patients. One of the most common complications of thoracentesis is pneumothorax, which has been reported to occur in 20% to 39% of thoracenteses, with 15% to 50% of patients with pneumothorax requiring tube thoracostomy.The present study was carried out to assess whether thoracenteses in cancer patients performed with ultrasound (US) guidance are associated with a lower rates of pneumothorax and tube thoracostomy than those performed without US guidance. METHODS: A total of 445 patients were recruited in this retrospective study. The medical records of 445 consecutive patients with cancer and MPE evaluable for this study, undergoing thoracentesis at the Oncology-Hematology and Internal Medicine Departments, Piacenza Hospital (Italy) were reviewed. RESULTS: From January 2005 to December 2011, in 310 patients (69.66%) thoracentesis was performed with US guidance and in 135 (30.34%) without it. On post-thoracentesis imaging performed in all these cases, 15 pneumothoraces (3.37%) were found; three of them (20%) required tube thoracostomy. Pneumothorax occurred in three out of 310 procedures (0.97%) performed with US guidance and in 12 of 135 procedures (8.89%) performed without it (P<0.0001). It must be emphasized that in all three patients with pneumothorax requiring tube thoracostomy, thoracentesis was performed without US guidance. CONCLUSIONS: The routine use of US guidance during thoracentesis drastically reduces the rate of pneumothorax and tube thoracostomy in oncological patients, thus improving safety as demonstrated in this study.

Ultrasound-guided Central Venous Catheterization for Home Parenteral Nutrition and Hydratation in Advanced Incurable Cancer Patients: Results of A Prospective Observational Study.

BACKGROUND: Most patients with advanced cancer are frequently malnourished and frequently they develop decreased oral fluid intake and dehidratation. Home parenteral nutrition (HPN) is an increasingly used therapy for patients with advanced cancer. A central venous access device is often an essential component allowing parenteral nutrition and hidratation. However central venous catheter (CVC) insertion represents a risk for pneumothorax or other mechanical complications. This study aimed to determine the reduction of risks related to central venous catheter positionement in the setting of cancer patients with palliative programm. METHODS: Consecutive patients with a variety of cancer in advanced phase requiring palliative care who were undergoing placement of central venous catheter for parenteral nutrition or hydratation have been prospectively studied in a program of ultrasound-guided CVC placement. Four types of possible complications were defined:mechanical, thrombotic, infection and malfunctioning. After sterilization, local anesthesia is applied and a 7.5 MHZ puncturing US probe is placed in the supraclavicular site and a 16-gauge needle is advanced under real-time US guidance, into the last portion of internal jugular vein by experienced physicians. The Seldinger tecnique is used to place the catheter that is advanced into the superior vena cava until insertion to right atrium. Two hours after each procedure a chest X-ray and US scanning are carried out to confirm CVC position and rule out a pneumotorax. RESULTS: From 30 October 2000 to 31 October 2008: 209 CVC insertional procedure were applied in 207 patients with cancer in the palliative phase only. There were 101 women and 106 men with a mean age of 67.68 year (range 22-86). A single needle puncture of the vein was performed on 206 of 209 procedures (98.6%), the technique was efficacious at the first attempt in 98.6% of cases, in 2 patients (0.96%) the CVC was positioned at the second attempt. The procedure failed only one case (0.44%). No cases of pneumothorax, of major bleeding or nerve punctured were reported. Symptomatic vein thrombosis developed in one patient (0.44%). Infection episodes were reported in two cases. Mean time for CVC permanence was 92.5±9.1 days (range 8-158). CONCLUSION: This study indicates that US-guided CVC insertion is a safe, cheap procedure for cancer patients in advanced phase and with palliative program, allowing parenteral nutrition and hydratation.

Ultrasound-guided central venous catheterization in cancer patients improves the success rate of cannulation and reduces mechanical complications: a prospective observational study of 1,978 consecutive catheterizations.

BACKGROUND: A central venous catheter (CVC) currently represents the most frequently adopted intravenous line for patients undergoing infusional chemotherapy and/or high-dose chemotherapy with hematopoietic stem-cell transplantation and parenteral nutrition. CVC insertion represents a risk for pneumothorax, nerve or arterial punctures. The aim of this prospective observational study was to explore the safety and efficacy of CVC insertion under ultrasound (US) guidance and to confirm its utility in clinical practice in cancer patients. METHODS: Consecutive adult patients attending the oncology-hematology department were eligible if they had solid or hematologic malignancies and required CVC insertion. Four types of possible complication were defined a priore: mechanical, thrombotic, infection and malfunctioning. The patient was placed in Trendelenburg's position, a 7.5 MHZ puncturing US probe was placed in the supraclavicular site and a 16-gauge needle was advanced under real-time US guidance into the last portion of internal jugular vein. The Seldinger technique was used to place the catheter, which was advanced into the superior vena cava until insertion into right atrium. Within two hours after each procedure, an upright chest X-ray and ultrasound scanning were carried out to confirm the CVC position and to rule out a pneumotorax. CVC-related infections, symptomatic vein thrombosis and malfunctioning were recorded. RESULTS: From December 2000 to January 2009, 1,978 CVC insertional procedures were applied to 1,660 consecutive patients. The procedure was performed 580 times in patients with hematologic malignancies and 1,398 times those with solid tumors. A single-needle puncture of the vein was performed on 1,948 of 1,978 procedures (98.48%); only eighteen attempts among 1,978 failed (0.9%). No pneumotorax, no major bleeding, and no nerve puncture were reported; four cases (0.2%) showed self-limiting hematomas. The mean lifespan of CVC was 189.7 +/- 18.6 days (range 7-701). Symptomatic deep-vein thrombosis of the upper limbs developed in 48 patients (2.42%). Catheter-related infections occurred in 197 (9.96%) of the catheters inserted. They were successfully treated with antibiotics and only in 48 (2.9%) patients definitive CVC removal was required for infection and/or thrombosis or malfunctioning. CONCLUSIONS: This study represents the largest published series of consecutive patients with cancer undergoing CVC insertion under US guidance; this procedure allowed the completion of the therapeutic program for 1,930/1,978 (97.6%) of the catheters inserted. The absence of pneumotorax and other major complications indicates that US guidance should be mandatory for CVC insertion in patients with cancer.

A case of Mycobacterium avium complex infection in an immunocompetent man presenting with pericarditis and an HRCT pattern of lymphangitis.

Non-tuberculous mycobacterial infections are rare in immunocompetent subjects. We describe the case of a 47-year-old previously healthy man with a Mycobacterium avium complex infection presenting with acute pericarditis and an atypical radiological pattern of lymphangitis.

Role of image-guided fine-needle aspiration biopsy in the management of patients with splenic metastasis.

BACKGROUND: Splenic metastases are very rare and are mostly diagnosed at the terminal phase of the disease or at the time of autopsy. The cytohistological diagnosis, when done, is made prevalently by splenectomy. Reports on splenic percutaneous biopsies in the diagnosis of splenic metastasis are fragmentary and very poor. The aims of this study are to analyse retrospectively the accuracy, safety and the clinical impact of ultrasound (US)-guided fine-needle aspiration biopsy (UG-FNAB) in patients with suspected splenic metastasis. METHODS: A retrospective analysis of 1800 percutaneous abdominal biopsies performed at our institute during the period from 1993 to 2003 was done and 160 patients that underwent splenic biopsy were found. Among these 160 patients, 12 cases with the final diagnosis of solitary splenic metastases were encountered and they form the basis of this report. The biopsies were performed under US guidance using a 22-gauge Chiba needle. All the patients underwent laboratory tests, CT examination of the abdomen and chest, US examination of abdomen and pelvis. RESULTS: There were 5 women and 7 men, median age 65 years (range 48-80). Eight patients had a known primary cancer at the time of the diagnosis of splenic metastasis: 3 had breast adenocarcinoma, 2 colon adenocarcinoma, 2 melanoma and 1 lung adenocarcinoma. Four patients were undiagnosed at the time of the appearance of splenic metastasis and subsequent investigations showed adenocarcinoma of the lung in 2 patients and colon adenocarcinoma in the remaining 2. There was a complete correspondence between the US and Computed Tomography (CT) in detecting focal lesions of the spleen. The splenic biopsies allowed a cytological diagnosis of splenic metastasis in all the 12 patients and changed clinical management in all cases. Reviewing the 160 patients that underwent UG-FNAB of the spleen we found no complications related to the biopsies. CONCLUSION: These results indicate that UG-FNAB is a successful technique for diagnosis of splenic metastasis allowing an adequate treatment of the affected patients.

Pulmonary hypertension is frequent in hyperthyroidism and normalizes after therapy.

BACKGROUND: In recent years, many authors have described several cases revealing an association between hyperthyroidism and pulmonary hypertension. This observational study was designed to evaluate the prevalence of pulmonary hypertension in hyperthyroidism and to determine the role of methimazole in regulating pulmonary vascular resistance in these patients. METHODS: We studied 114 patients, 78 women and 36 men, whose mean age was 51+/-13years. Forty-seven had Graves' disease and 67 had a nodular goiter. All subjects were ambulatory and were recruited in a consecutive order. The control group (group 2) included 20 healthy subjects matched for age and sex. Transthoracic Doppler echocardiography was performed and systolic pulmonary artery pressure (PAPs) was determined by the tricuspid regurgitation method using the Bernoulli's equation. We performed a 120-day follow-up in the patients with pulmonary hypertension and we divided them into two subgroups: group 1A (n=33), patients treated with methimazole, and group 1B (n=17), subjects treated with partial thyroidectomy. RESULTS: We found a mild pulmonary hypertension in 50 patients in group 1 (43%) and in none of those in the control group. The mean+/-SD PAPs was 27.77+/-6.56 in group 1 and 21.32+/-2.55 in group 2. A negative correlation was found between the T.S.H. value and the level of PAPs (r=-0.85; p<0.001). During the follow-up, group 1A went from a PAPs value of 34.3+/-3.2 to 29.2+/-3.3 after 15days of therapy and group 1B from 34.3+/-3.0 to 34.1+/-2.9 (p<0.001). CONCLUSIONS: The results of the present study demonstrate a frequent association between hyperthyroidism and mild and transient pulmonary hypertension. Subjects treated with methimazole have a more rapid drop in PAPs.

[Thrombotic thrombocytopenic purpura: report of seven cases]. / Porpora trombotica trombocitopenica: descrizione di sette casi.

From May 1999 to January 2002 we observed 7 patients (4 females and 3 males, median age 55 years, range 31-81 years) with thrombotic thrombocytopenic purpura (TTP). Six patients has been previously undiagnosed and 1 patient was at second relapse. Trigger factors of TTP were identified in 6 patients: ticlopidine treatment (2 patients); an acute cutaneous infection episode immediately before the features of TTP (1 patient); presence of devices: orthodontic (1 patient) and intrauterine contraceptive (1 patient), Mycoplasma urealyticum vaginal infection (1 patient). In all the 7 patients the clinical status was mainly related to the hemolytic anemia, thrombocytopenia and neurological events. One of these patients presented with hemolytic-uremic syndrome with acute renal failure and macrohematuria at onset, another one showed a systemic exanthema post-infection-like. Six out of 7 patients presented with different neurological events: headache, confusion, focal neurological failure. All the 7 patients were promptly treated with plasma-exchange and cryosupernatant plasma infusion. In addition they received prednisone 25-50 mg/day. All the 7 patients achieved a complete remission after plasma-exchange, one relapsed 3 months later and was treated with plasma-exchange again. All the patients are in complete remission with a median follow-up of 36.3 months (range 20-62 months). From these cases we suggest: 1) clinicians should take in mind the suspicion of TTP in every patient with hemolytic, negative direct Coombs test, anemia, thrombocytopenia, high level of lactate dehydrogenase; 2) the treatment of choice is plasma-exchange; 3) the response of treatment is good if therapy is promptly and aggressively administered; 4) the possible role of a trigger factor for removing it and to prevent relapses.

Pulmonary involvement in inflammatory bowel disease.

Inflammatory bowel disease is a systemic illness that may involve the lung. The most frequent manifestation is bronchial inflammation and suppuration with or without bronchiectasis. Bronchoalveolar lavage data show an increase percentage of neutrophils and steroids are very effective in the majority of cases. Some patients present severe tracheal inflammation and obstruction with an inflammatory mass bulging into the tracheal lumen. Others show a small airway involvement with or without bronchiolitis obliterans organizing pneumonia pattern and have an equivocal response to steroids. In recent years many investigators demonstrated latent pulmonary involvement with a reduction in lung transfer factor and a small airways disorders.

[Thyroid dysfunction and pulmonary hypertension]. / Distiroidismi e ipertensione polmonare.

Prior observational studies and several case reports have suggested an association between thyroid dysfunction and pulmonary hypertension. This review was designed to evaluate the prevalence and the pattern of pulmonary vasculature involvement in hyper- and hypothyroidism. We identified original research papers and reviews by going through leading journals that publish basic and clinical research in the fields of pulmonary hypertension, hyperthyroidism and hypothyroidism, by electronically searching the Medline database. We directed special attention to papers published from 1972 to 2003. Our findings indicate the presence of a frequent association between hyperthyroidism and pulmonary hypertension (35% in the largest series of cases) which decrease after achievement of a euthyroid state. A possible explanation includes an influence of thyroid hormones which affect growth and maturation of vascular cells and enhanced catecholamine sensitivity causing pulmonary vasoconstriction. Furthermore, several studies suggest a high prevalence of transient pulmonary hypertension in hypothyroidism (49% in the largest series of cases), in these cases autoimmunity play a key role.

Advanced waldenström's macroglobulinemia: a case of possible cure after systemic chemotherapy, splenic radiation and splenectomy.

A 41-year-old man with advanced Waldenström's macroglobulinemia (WM) associated with the hyperviscosity syndrome, massive splenomegaly and with IgM concentration of 10 g/dl, was treated in January 1984 with plasmapheresis, systemic chemotherapy (M2 protocol) and splenic radiotherapy. He rapidly improved and was discharged 1 month later. Fourteen months later he underwent splenectomy since a mild splenomegaly persisted though the normalization of bone marrow, peripheral blood and electrophoresis with an IgM concentration of 140 mg/dl. However, at this time immunofixation and immunoelectrophoresis showed a small IgM-kappa monoclonal component. The histological and immunohistochemical analysis showed minimal splenic involvement by WM. Two months after splenectomy, immunofixation and immunoelectrophoresis showed no monoclonal component. The spleen was the probable site of minimal residual disease. The patient was treated with monthly chlorambucil and prednisone for 2 years. Subsequently clinical and laboratory tests persisted within normal limits. The last control performed in January 2002 showed that the patient was in good health; bone marrow examination (aspiration, biopsy with immunohistochemical analysis) and immunofixation persisted normally. This interesting case report, with advanced WM, alive, in good health and without signs of disease 18 years from diagnosis, is presented here and the role of splenectomy is debated.