Drug-induced interstitial lung disease during cancer therapies: expert opinion on diagnosis and treatment.

BACKGROUND: Drug-induced interstitial lung disease (DIILD) is a form of interstitial lung disease resulting from exposure to drugs causing inflammation and possibly interstitial fibrosis. Antineoplastic drugs are the primary cause of DIILD, accounting for 23%-51% of cases, with bleomycin, everolimus, erlotinib, trastuzumab-deruxtecan and immune checkpoint inhibitors being the most common causative agents. DIILD can be difficult to identify and manage, and there are currently no specific guidelines on the diagnosis and treatment of DIILD caused by anticancer drugs. OBJECTIVE: To develop recommendations for the diagnosis and management of DIILD in cancer patients. METHODS: Based on the published literature and their clinical expertise, a multidisciplinary group of experts in Italy developed recommendations stratified by DIILD severity, based on the Common Terminology Criteria for Adverse Events. RESULTS: The recommendations highlight the importance of multidisciplinary interaction in the diagnosis and management of DIILD. Important components of the diagnostic process are physical examination and careful patient history-taking, measurement of vital signs (particularly respiratory rate and arterial oxygen saturation), relevant laboratory tests, respiratory function testing with spirometry and diffusing capacity of the lung for carbon monoxide and computed tomography/imaging. Because the clinical and radiological signs of DIILD are often similar to those of pneumonias or interstitial lung diseases, differential diagnosis is important, including microbial and serological testing to exclude or confirm infectious causes. In most cases, management of DIILD requires the discontinuation of the antineoplastic agent and the administration of short-term steroids. Steroid tapering must be undertaken slowly to prevent reactivation of DIILD. Patients with severe and very severe (grade 3 and 4) DIILD will require hospitalisation and often need oxygen and non-invasive ventilation. Decisions about invasive ventilation should take into account the patient's cancer prognosis. CONCLUSIONS: These recommendations provide a structured step-by-step diagnostic and therapeutic approach for each grade of suspected cancer-related DIILD.

Strategies to tackle RAS-mutated metastatic colorectal cancer.

The RAS oncogene is among the most commonly mutated in cancer. RAS mutations are identified in about half of patients diagnosed with metastatic colorectal cancer (mCRC), conferring poor prognosis and lack of response to anti-epidermal growth factor receptor (EGFR) antibodies. In the last decades, several investigational attempts failed in directly targeting RAS mutations, thus RAS was historically regarded as 'undruggable'. Recently, novel specific KRASG12C inhibitors showed promising results in different solid tumors, including mCRC, renewing interest in this biomarker as a target. In this review, we discuss different strategies of RAS targeting in mCRC, according to literature data in both clinical and preclinical settings. We recognized five main strategies focusing on those more promising: direct RAS targeting, targeting the mitogen-activated protein kinase (MAPK) pathway, harnessing RAS through immunotherapy combinations, RAS targeting through metabolic pathways, and finally other miscellaneous approaches. Direct KRASG12C inhibition is emerging as the most promising strategy in mCRC as well as in other solid malignancies. However, despite good disease control rates, tumor response and duration of response are still limited in mCRC. At this regard, combinational approaches with anti-epidermal growth factor receptor drugs or checkpoint inhibitors have been proposed to enhance treatment efficacy, based on encouraging results achieved in preclinical studies. Besides, concomitant therapies increasing metabolic stress are currently under evaluation and expected to also provide remarkable results in RAS codon mutations apart from KRASG12C. In conclusion, based on hereby reported efforts of translational research, RAS mutations should no longer be regarded as 'undruggable' and future avenues are now opening for translation in the clinic in mCRC.

Ulipristal Acetate Efficacy in a Patient with Symptomatic Fibroid and Concomitant Pulmonary Embolism.

Ulipristal acetate (UPA) is an effective drug for the treatment of symptomatic uterine fibroids. The drug is highly effective in controlling bleeding control and in the recovery of anemia. Here, we report the case of a woman with severe menorrhagia due to a uterine fibroid and with concomitant pulmonary embolism, a serious life-threatening condition. UPA was shown to be effective in reducing fibroid volume and controlling symptoms, without worsening the underlying embolic disease. No adverse events were observed, and the patient has completely recovered.

[Working with families in the early stages of psychosis: a structured intervention for caregivers]. / Lavorare con le famiglie negli esordi psicotici: un intervento strutturato per i caregiver.

In the field of early psychosis psychoeducation is considered fundamental to increase coping skills with diseases and to improve the quality of life of patients and their families. The more recent and updated guidelines on schizophrenia underline the extreme importance of the families involvement in treatment of young people in the initial phases of illness. "Families are the main support for many young patients. They could be the primary carers but they have also to face individual and social consequences following the onset course. Where feasible, family members must be involved in the treatment". This work describes the components of the work with families carried on by the Centre for the early detection of psychoses and high-risk situations--Programma 2000 ("Niguarda Ca' Granda" Hospital-Milan) and is mostly focused on psychoeducation and on Expressed Emotions aspects. Even the advances suggested by the international literature drove Programma 2000 to define both the steps of caregivers assessment and intervention. During the last ten years, Programma 2000 has followed 191 caregivers. Aims of this work is to verifier the outcome of the "pilot project", started in 2007, projected specifically to increase the normally used strategies to improve the caregivers adherence and involvement in the therapeutic process. The individualized multi-componential intervention has been structured in 8 session over one years. Outcome measures used in this article are the scores of the Camberwell Family Interview and from the Psychosis Knowledge Assessement Semistructured Interview (VCP). The subjects enrolled in the structured pilot project were 25 family caregiver to young (18-30 yrs old) patients. Results shows change in the Expressed Emotion level: 13% of families moved from High Expressed Emotion to Low Expressed Emotion. Furthermore data on the knowledge of illness knowledge level illustrate a reduction in the percentage, from 47% to 18%, of carers who have just a very vague knowledge of illness, and an increase from 16% to 27% of carers who obtain a good level of specific knowledge. In conclusion we can sustain mental health expert with aim to treatment project programme individualized and multi-componential tailored for young's caregiver at the onset phase of psychosis.

Outcomes and Risk Factors for Complications of Laser Ablation for Thyroid Nodules: A Multicenter Study on 1531 Patients.

BACKGROUND: Image-guided laser ablation therapy (LAT) of benign thyroid nodules demonstrated favorable results in randomized trials with fixed modalities of treatment. The aim of this retrospective multicenter study was to assess the effectiveness, tolerability, and complications of LAT in a large consecutive series of patients from centers using this technique in their routine clinical activity. PATIENTS: Clinical records of 1534 consecutive laser-treated nodules in 1531 patients from eight Italian thyroid referral centers were assessed. Inclusion criteria were as follows: solid or mixed nodules with fluid component up to 40%; benign cytological findings; and normal thyroid function. METHODS: LAT was performed with a fixed-power protocol, whereas the number of applicators and illumination times were different according to target size. From one to three illuminations with pullback technique and with a total energy delivery based on the nodule volume were performed during the same session. Patients were evaluated during LAT, within 30 days, and 12 months after the procedure. RESULTS: Total number of treatments was 1837; 1280 (83%) of nodules had a single LAT session. Mean nodule volume decreased from 27 ± 24 mL at baseline to 8 ± 8 mL 12 months after treatment (P < .001). Mean nodule volume reduction was 72% ± 11% (range 48%-96%). This figure was significantly greater in mixed nodules (79% ± 7%; range 70%-92%) because they were drained immediately before laser illumination. Symptoms improved from 49% to 10% of cases (P < .001) and evidence of cosmetic signs from 86% to 8% of cases (P < .001). Seventeen complications (0.9%) were registered. Eight patients (0.5%) experienced transitory voice changes that completely resolved at the ear-nose-throat examination within 2-84 days. Nine minor complications (0.5%) were reported. No changes in thyroid function or autoimmunity were observed. CONCLUSIONS: Real practice confirmed LAT as a clinically effective, reproducible, and rapid outpatient procedure. Treatments were well tolerated and risk of major complications was very low.

Stereotactic excisional breast biopsy performed by interventional radiologists using the advanced breast biopsy instrumentation system.

The Advanced Breast Biopsy Instrumentation (ABBI) system, which uses surgical cannulas up to 20 mm in diameter, is an alternative to conventional surgical biopsy for the diagnosis of non-palpable breast lesions. Since the need for radiological skill outweighs the surgical content of the technique, we evaluated the feasibility of complete management of the procedure by interventional radiologists. 35 of the 111 patients originally scheduled for the procedure were excluded, three because the lesion could not be visualized and 32 because of insufficient thickness of the compressed breast. The procedure had to be abandoned in one case due to a technical failure. 77 stereotactic excisional breast biopsy procedures were performed using the ABBI system in 75 patients with suspicious non-palpable mammographic lesions. The procedure was carried out under local anaesthesia in the radiology department, using a dedicated Lorad (R) radiographic system. 31 (40%) masses without calcifications, 11 (14%) masses with calcifications and 35 (46%) clusters of microcalcifications without tumour mass were sampled. 43 (56%) benign lesions and 34 (44%) malignant lesions were diagnosed. The overall mean diameter of the lesions was 8.7 mm (range 3-22 mm). All 34 patients with malignancies and lobular carcinoma in situ subsequently underwent surgery, the results of which are reported. Three (4%) haematomas were detected and aspirated percutaneously. Two technical problems occurred: an ABBI cannula malfunction, and a computer failure of the digital imaging system during the procedure. The average procedure time was 80 min and the cost of each procedure was 2,800,000 Italian lire (1555 US$). It is concluded that tissue sampling with the ABBI system can be performed entirely by radiologists without significant problems. The procedure was well tolerated by all patients. The quality of the biopsy specimen was identical to that of a surgical specimen but with the advantages of stereotactic precision for localization of the lesion.

Long-term infusion in cancer chemotherapy with the Groshong catheter via the inferior vena cava.

AIMS AND BACKGROUND: Vascular access through a vein draining into the superior vena cava is commonly used for long-term infusion of drugs inr cancer chemotherapy; prolonged cannulation of the inferior vena cava is generally considered as having an excessively high complication rate. METHODS: Prolonged cisplatin infusion via the inferior vena cava by means of a Groshong catheter was evaluated in 20 consecutive patients with thoracic malignancies showing evidence of superior vena cava infiltration or obstruction. RESULTS: We achieved 1,291 catheter days for our survey with a mean duration of vascular access of 64.5 days per patient and a mean duration of infusion time of 40 days. There were 2 complications, a catheter obstruction after a 7-day rest period and an ileo-femoral thrombosis 6 days after catheter placement. CONCLUSIONS: Our experience compared favourably with the results obtained by long-term central venous access via the supraumbilical route, and demonstrated the reliability and safety of this approach in cases where the superior vena cava cannulation is technically difficult or impossible.

Carbon dioxide digital subtraction angiography in oncological-interventional radiology.

AIMS AND BACKGROUND: The aim of this work is to demonstrate the usefulness of carbon dioxide, used as contrast agent, in special indications in vascular interventional oncological procedures. METHODS: We studied 40 patients with digital subtraction angiography enhanced with CO2 as a contrast agent. At the same time we utilized also, in all cases, jodinated contrast agent to evaluate the different opacification gradient, the different viscosity range and the different perfusion. RESULTS: The low viscosity of CO2 allows demonstration of the presence of even minimal blood losses in gastrointestinal tumors and enhances arteriovenous shunts in hepatocellular carcinoma. Carbon dioxide can also be employed to assess the patency of small-sized catheters for chemotherapy infusion which do not allow easy injection of the traditional iodinated contrast agents characterized by high viscosity. CONCLUSION: Carboangiographic study combined to digital subtraction angiography can clear some diagnostic problems and is further method to assess the outcome of angiographic interventional procedures in oncology.

[Total parenteral nutrition in packages. Methods of application in a general surgery department]. / Nutrizione parenterale totale in sacca. Metodiche di applicazione in un reparto di chirurgia generale.

In the period June 1987-March 1988, 80 patients classifiable according to ASPEN criteria were submitted to Total Parenteral Nutrition (TPN) using a single package nutrient mixing technique. The problems relating to the compatibility and stability of the solution are analysed and a protocol is proposed for the preparation of packages and the management of the central venous catheter compatible with the needs of a general surgery department. Personal experience has enabled us to observe the undoubted advantages of this technique: reduction of the time necessary for nursing the TPN patient, greater reliability in controlling speed of infusion and infectious complications, greater comfort for the patient.

[Non-traumatic colic perforation in free peritoneum. Apropos of 61 cases]. / Perforazioni coliche non traumatiche in peritoneo libero. A proposito di 61 casi.

Sixty-one non-traumatic perforations in free peritoneum are reported. The principal aetiology is diverticulitis (35 cases) followed by cancer (22 cases). 18 derivations were carried out, 34 colectomies without anastomosis, 5 ideal colectomies and 4 diverticulectomies. Total mortality was 19.7-14% for diverticulitis, 22.2% for perforations at the cancer site, 50% from diastasic perforations. Stress is laid on the need to treat colic perforation by colectomy without anastomosis, confining derivation openeum. Sixty-one cases.

[Endometriosis on a cesarean cicatrix. Apropos of 3 cases]. / Endometriosi su cicatrice per cesareo. A proposito di tre casi.

Endometriosis on a caesarean scar is a well-known, though not frequent event. The lesion generally presents as a painful nodule of the abdominal wall during the menstrual cycle. Pain cyclicity is a useful sign for diagnosis. Treatment consists of removal. Three cases are reported.

[A splenic autograft in omental pockets following splenectomy for trauma. The authors' personal experience of 10 cases]. / Autotrapianto splenico su tasche omentali dopo splenectomia per trauma. Esperienza personale su 10 casi.

Personal experience on 10 patients splenectomised for trauma and subjected to splenic autotransplantation on omental pockets is reported. After describing autotransplant candidate selection criteria and the surgical technique followed, the flattering results are reported. Particularly interesting was the fact that no local suppuration was encountered and the transplant took in all patients, as demonstrated by scans carried out with labelled red globules and radiocolloid.

[Retroperitoneal leiomyosarcoma (case report)]. / Leiomiosarcoma retroperitoneale (Case report).

After a short introduction about the retroperitoneal tumors classification the Authors write on the management of this tumor. They present their case report: surgical treatment of retroperitoneal leiomyosarcoma. Actually the role of surgical strategy in the management of resectable retroperitoneal tumors is the most important than adjuvant therapy, even if the surgery must be very demolitive.

[Intra-abdominal rupture of varices of the round ligament: a rare cause of hemoperitoneum in patients with cirrhosis]. / La rottura intra-addominale di varici del ligamento rotondo: rara causa d'emoperitoneo nel cirrotico.

The authors report two cases of haemoperitoneum due to intra-abdominal rupture of the round ligament in cirrhotic patients with portal hypertension. A review of the literature on the subject reveals the rarity of such observations. The eventuality must be borne in mind, however, in the treatment of the haemorrhagic complications of portal hypertension in view of the associated high mortality. Simple ligature of the bleeding varix is the operation which offers the greatest possibility of survival.

[Traumatic chylothorax (apropos of a case following a closed vertebral-thoracic injury)]. / Chilotorace traumatico (a proposito di un caso consecutivo a trauma chiuso vertebro-toracico).

The authors report a case of chylothorax due to blunt trauma with fracture of the spine in a man aged 60. After mentioning the possible pathogenesis and clinics of the case shown, the Authors explain the treatment successfully adopted, that is, the ligature of thorax duct at his inlet in the thorax through right thoracotomy on the 5th intercostal space.

[Lesions caused by the ingestion of caustics]. / Lesioni da ingestione di caustici.

The diagnostic and therapeutic approach to the maiagement of lesions caused by ingestion of caustic substances has made substantial progress in the past few years and has now been codified. The linch-pins of the present approach are emergency endoscopy for an immediate assessment of the lesions and total parenteral nutrition to reduce the morbidity in patients whose lesions may be expected to take a long time to heal or may require surgical repair. The diagnostic and therapeutic protocol advocated derives from a close examination of the literature and from personal experience.

[Recent traumatic rupture of the diaphragm in patients with multiple injuries]. / Le rotture traumatiche recenti del diaframma nei politraumatizzati.

The authors report on 16 cases of recent traumatic diaphragmatic lesions in polytraumatized patients referred to them over the period 1979-86. After examining the diagnostic problems relating to this type of lesion, the authors describe the anatomico-topographical, clinical and therapeutic aspects. They conclude by stressing the need to explore the diaphragmatic cupulae systematically in the course of surgery for blunt abdominal trauma.

[Hemorrhages of the lower digestive tract: the diagnostic and therapeutic approach]. / Emorragie del tratto digestivo inferiore: approccio diagnostico e terapeutico.

The authors describe their experience with colo-rectal haemorrhage. They stress the tendency towards spontaneous arrest of such haemorrhages (92.6% of cases) as the usefulness of emergency colonoscopy in diagnosing the cause and/or site of the haemorrhagic lesion (85.7% of positive results in the present series). Therapy may be conservative (endoscopic or in the course of angiography) or surgical. Surgery is indicated in cases failing to respond to conservative therapy and in cases of unarrestable haemorrhage and usually consists in segmental resection of the portion of the intestinal tract involved.

[Pulmonary carcinosarcoma]. / Carcinosarcoma polmonare.

Sarcomatoid carcinomas of the lung are uncommon neoplasms; the concurrent presence of malignant epithelial and sarcomatoid spindle cell components show a high malignancy. Lymph node metastases at presentation is an important prognostic factor, on the other way the most patients with sarcomatoid carcinoma of the lung usually presented at an advanced stage that needed a complementary therapy. The Authors report about one surgical case of pulmonary carcinosarcoma recently observed without lymph node metastases; the literature is reviewed and the histogenesis is discussed.

[Leiomyosarcoma of the Meckel's diverticulum (presentation of a new case)]. / Il leiomiosarcoma del diverticolo di Meckel (segnalazione di un nuovo caso).

A new case of Meckel's leiomyosarcoma is described. The rarity of the disease, the problems of differential diagnosis and the difficulty of establishing the malignant nature of the condition and thus the prognosis justify the report together with a review of the most recent literature.