Abstract Background The healing of hemorrhoidectomy wounds is a main concern of surgeons and patients. Various modalities can improve the quality of wound care after surgery. Several types of surgery, antibiotics and topical agents, such as solutions and ointments, have been evaluated. The current research investigates the effects of cleansing cream in the post – operative management after open diathermy hemorrhoidectomy in terms of wound healing and post – operative pain. Methods Between January 2022 and December 2022, 70 consecutive patients underwent open diathermy hemorrhoidectomy for III- and IV- degree hemorrhoids using a cleansing cream postoperatively and were evaluated. Results 70 patients with third- (n = 46, 65%) and fourth- degree (n = 24, 35%) hemorrhoids were consecutively enrolled. The mean operative time was 21 minutes (range, 17 to 41 min). No intraoperative complications were detected. HSS and VAS score decreased over the time and all patients achieved complete wound healing at the last follow-up despite three of these developed posterior anal fissure. All patients had returned to normal activities (range, 10 days to 15 days). Conclusion The results suggest the safety and the effectiveness in terms of post operative pain and wound healing of cleansing crema after open diathermy hemorrhoidectomy. Further multicenter study comparing different ointments are needed to confirm this finding.

Anemia is frequently present in patients with myelofibrosis (MF), and it may be exacerbated by treatment with the JAK2-inhibitor ruxolitinib (RUX). Recently, a relevant blast phase (BP) incidence has been reported in anemic MF patients unexposed to RUX. The authors investigated the incidence of BP in 886 RUX-treated MF patients, included in the "RUX-MF" retrospective study. The BP incidence rate ratio (IRR) was 3.74 per 100 patient-years (3.74 %p-y). At therapy start, Common Terminology Criteria for Adverse Events grade 3-4 anemia (hemoglobin [Hb] <8g/dL) and severe sex/severity-adjusted anemia (Hb <8/<9g/dL in women/men) were present in 22.5% and 25% patients, respectively. IRR of BP was 2.34 in patients with no baseline anemia and reached respectively 4.22, 4.89, and 4.93 %p-y in patients with grade 1, 2, and 3-4 anemia. Considering the sex/severity-adjusted Hb thresholds, IRR of BP was 2.85, 4.97, and 4.89 %p-y in patients with mild/no anemia, moderate, and severe anemia. Transfusion-dependent patients had the highest IRR (5.03 %p-y). Progression-free survival at 5years was 70%, 52%, 43%, and 27% in patients with no, grade 1, 2, and 3-4 anemia, respectively (p<.001). At 6months, 260 of 289 patients with no baseline anemia were receiving ruxolitinib, and 9.2% had developed a grade 3-4 anemia. By 6-month landmark analysis, BP-free survival was significantly worse in patients acquiring grade 3-4 anemia (69.3% vs. 88.1% at 5years, p<.001). This study highlights that anemia correlates with an increased risk of evolution into BP, both when present at baseline and when acquired during RUX monotherapy. Innovative anemia therapies and disease-modifying agents are warranted in these patients.

Colorectal cancer is a frequent neoplasm in western countries, mainly due to dietary and behavioral factors. Its incidence is growing in developing countries for the westernization of foods and lifestyles. An increased incidence rate is observed in patients under 45 years of age. In recent years, the mortality for CRC is decreased, but this trend is slowing. The mortality rate is reducing in those countries where prevention and treatments have been implemented. The survival is increased to over 65%. This trend reflects earlier detection of CRC through routine clinical examinations and screening, more accurate staging through advances in imaging, improvements in surgical techniques, and advances in chemotherapy and radiation. The most important predictor of survival is the stage at diagnosis. The screening programs are able to reduce incidence and mortality rates of CRC. The aim of this paper is to provide a comprehensive overview of incidence, mortality, and survival rate for CRC.

Chronic myeloid leukemia (CML) has evolved from an invariably fatal disease to a chronic disorder that can be treated with targeted drugs and allows survival expectations approaching age-matched controls. Thus, pregnancy and conception in CML should not be precluded anymore; however, to ensure the well-being of both the mother and the developing fetus careful planning and management are required. Tyrosine Kinase Inhibitors (TKIs) are not genotoxic or carcinogenic but can pose a risk to the developing fetus, due to their teratogenic potential. The risk depends on the TKI and the stage of fetal development during exposure. Teratogenic risk is high in the first trimester of pregnancy when the baby's organs and structures are forming (5-12 weeks). If a female patient is on therapy it is advisable to stop therapy at the first positive pregnancy test (3-5 weeks) to maximize the length of treatment-free, and ideally to not treat until delivery. If needed, the medication plan during pregnancy may be adjusted. Interferons can be used at any time, imatinib and nilotinib have a reduced placental crossing and could be carefully used after 16 weeks, whereas dasatinib crosses the placenta and can induce problems throughout the whole gestation. Management of pregnancy in CML is complex. This manuscript is an update of the state of the art allowing healthcare providers to be informed of the different situations that can occur and their governance.

ABSTRACTBackgroundIn patients with atrial fibrillation (AF) on vitamin K antagonist (VKA) therapy and therapeutical INR range the incidence of cardiac thromboembolism is not negligible and the subgroup carrying a mechanical prosthetic mitral valve (PMV) has the highest risk. We aimed to assess the long-term effects of left atrial appendage closure (LAAC) in AF patients carriers of mechanical PMV who experienced a failure of VKA therapy.MethodsIn this retrospective, multicenter study, patients who underwent LAAC because of thrombotic events including TIA/stroke, systemic embolism and evidence of left atrial appendage thrombosis/sludge during VKA therapy were enrolled. Patients with mechanical PMV were included and compared with controls. The primary endpoint was the composite of all-cause death, major cardiovascular events and major bleedings at follow-up. Feasibility and safety of LAAC was also assessed.ResultsA total of 55 patients (42% females; mean age 70 ± 9 years) including 12 carriers of mechanical PMV were enrolled. The most frequent indication to LAAC (71%) was LAA thrombosis or sludge. Procedural success was achieved in 96% of overall cases and in 100% of patients with PMV. In 35 patients a cerebral protection device was used. During a median follow-up of 6.1 ± 4.3 years, 4 patients with PMV and 20 patients without PMV reported adverse events (HR 0.73 [95% CI 0.25 – 2.16, p=0.564]).ConclusionLAAC seems to be a valuable alternative in AF patients with failure of VKA therapy who are carriers of mechanical PMV. This off-label, real-world clinical practice indication deserve validation in further studies.

The primary aim of the European Society of Coloproctology (ESCP) Guideline Development Group (GDG) was to produce high-quality, evidence-based guidelines for the management of cryptoglandular anal fistula with input from a multidisciplinary group and using transparent, reproducible methodology. Previously published methodology in guideline development by the ESCP has been replicated in this project. The guideline development process followed the requirements of the AGREE-S tool kit. Six phases can be identified in the methodology. Phase one sets the scope of the guideline, which addresses the diagnostic and therapeutic management of perianal abscess and cryptoglandular anal fistula in adult patients presenting to secondary care. The target population for this guideline are healthcare practitioners in secondary care and patients interested in understanding the clinical evidence available for various surgical interventions for anal fistula. Phase two involved formulation of the GDG. The GDG consisted of 21 coloproctologists, three research fellows, a radiologist and a methodologist. Stakeholders were chosen for their clinical and academic involvement in the management of anal fistula as well as being representative of the geographical variation among the ESCP membership. Five patients were recruited from patient groups to review the draft guideline. These patients attended two virtual meetings to discuss the evidence and suggest amendments. In phase three, patient/population, intervention, comparison and outcomes questions were formulated by the GDG. The GDG ratified 250 questions and chose 45 for inclusion in the guideline. In phase four, critical and important outcomes were confirmed for inclusion. Important outcomes were pain and wound healing. Critical outcomes were fistula healing, fistula recurrence and incontinence. These outcomes formed part of the inclusion criteria for the literature search. In phase five, a literature search was performed of MEDLINE (Ovid), PubMed, Embase (Ovid) and the Cochrane Database of Systematic Reviews by eight teams of the GDG. Data were extracted and submitted for review by the GDG in a draft guideline. The most recent systematic reviews were prioritized for inclusion. Studies published since the most recent systematic review were included in our analysis by conducting a new meta-analysis using Review manager. In phase six, recommendations were formulated, using grading of recommendations, assessment, development, and evaluations, in three virtual meetings of the GDG. In seven sections covering the diagnostic and therapeutic management of perianal abscess and cryptoglandular anal fistula, there are 42 recommendations. This is an up-to-date international guideline on the management of cryptoglandular anal fistula using methodology prescribed by the AGREE enterprise.

Background and objectivePatients with palpitations clinically suggestive of paroxysmal supraventricular tachycardia (PSVT) are often managed conservatively until ECG-documentation of the tachycardia, leading to high impact on life quality and healthcare resource utilisation. We evaluated results of electrophysiological study (EPS), and ablation when appropriate, among these patients, with special focus on gender differences in management. MethodsBELIEVE SVT is a European multi-centre, retrospective registry in tertiary hospitals performing EPS in patients with palpitations, without ECG-documentation of tachycardia or preexcitation, and considered highly suggestive of PSVT by a cardiologist or cardiac electrophysiologist. We analysed clinical characteristics, results of EPS and ablation, complications, and clinical outcomes during follow-up. Results680 patients from 20 centres were included. EPS showed sustained tachycardia in 60.9% of patients, and substrate potentially enabling AVNRT in 14.7%. No major/permanent complications occurred. Minor/transient complications were reported in 0.84% of patients undergoing diagnostic-only EPS and 1.8% when followed by ablation. During a 3.4-year follow-up, 76.2% of patients remained free of palpitations recurrence. Ablation (OR: 0.34, p<0.01) and male gender (OR: 0.58, p=0.01) predicted no recurrence. Despite a higher female proportion among patients with recurrence, (77.2% vs. 63.5% among those asymptomatic during follow-up, p<0.01), 73% of women in this study reported no recurrence of palpitations after EPS. ConclusionsEPS and ablation are safe and effective in preventing recurrence of non-documented palpitations clinically suggestive of PSVT. Despite a lower efficacy, this strategy is also highly effective among women and warrants no gender differences in management.

Background Digital health tools are increasingly being used in oncology practice to better monitor patients' health status. They may include electronic-patient-reported outcome (ePRO) monitoring systems, with automated alerts triggered to the physician depending on specific conditions (e.g., when patients report clinically relevant problems). Although implementation of these tools in real-life practice may offer valuable benefits, it is important to assess their usability and utility from the users' standpoint. Objective The aim of this study was to evaluate the patients' perception of usability and utility of a digital health tool for ePRO monitoring of patients with hematologic malignancies in real-life practice. Methods In December 2020, the GIMEMA Group developed a digital health platform for adult patients with hematologic malignancies (GIMEMA-ALLIANCE platform) with the goal of facilitating patient-centered care. The platform was open to enrollment until December 2022 and involved 26 hospitals. After providing written informed consent, patients received a personal password to access the secure patient portal and complete ePRO questionnaires assessing health-related quality of life (HRQoL) and symptoms (EORTC QLQ-C30 and selected items from the EORTC Item Library). Real-time graphical presentation of PRO results is displayed for both patients and physicians. The platform allows hematologists to receive real-time alerts in the presence of clinically important problems and symptoms. For the purpose of this study, a dedicated section in the patient portal was developed to evaluate the usability and utility of the platform. In this section, patients had the possibility to complete the System Usability Scale (SUS). The SUS is a 10-item widely used questionnaire to evaluate users' perceived system satisfaction. Its score ranges from 0 to 100 and a score ≥70 is considered a threshold for an acceptable usability. Analyses were performed overall and by age group category, based on the median age of the patient population. Patients also completed an ad-hoc survey consisting of 6 items covering aspects on the utility of the platform, for example in favoring shared decision-making or improving the communication with the treating hematologist. Only patients who have completed the ePRO questionnaires at least twice, i.e. those who had the possibility to sufficiently test its functionalities, were considered eligible for completing the survey on usability and utility of the platform. Results Out of the 362 eligible patients, a total of 161 (44%) completed the survey. No difference in age and sex was found between patients who completed or not the survey. The median age of patients who completed the survey was 59 years (IQR: 51 - 67) and 53 (34%) were women. The most prevalent diagnosis was multiple myeloma (n=40, 25%). At the time of survey completion, 69% of the patients were receiving a treatment for their disease. The mean SUS score of the overall population was 80.8 (SD 15.5) and the majority of patients (n=131, 81%) gave a rating ≥70 (the prespecified threshold for the acceptable usability). The mean SUS score for the younger and the older groups was 80.5 (SD 14.9) and 81.4 (SD 16), respectively. Eighty-eight percent of patients agreed or strongly agreed that the platform was easy to use, 83% felt very confident in using the platform, and 72% found the various functionalities offered by the platform well integrated (Figure 1). Positive feedbacks on the utility of the platform were also collected. For example, 71% of patients considered the ePRO questionnaires useful for their health conditions and 63% would recommend its use to other patients. However, amongst the patients who had visits at the clinic (n=127), only 39% reported that their doctor discussed ePRO results with them, and this may explain the lower agreement for some items (Figure 2). For example, 38% of the patients strongly agreed/agreed that the platform helped them to improve the communication with their doctor, while 44% neither agreed or disagreed and 18% strongly disagreed/disagreed. Conclusion This study showed a good usability and utility of the GIMEMA-ALLIANCE platform from the patients' perspective, and this was true for younger and older patients. Future areas of improvement should include actions to facilitate physicians in discussing ePRO results during the clinical encounter with their patients.

The goal of Treatment Free Remission (TFR) is achievable in no more than 25-30% of patients with Ph+ Chronic Myeloid Leukemia (CML) treated with Tyrosine Kinase Inhibitors (TKIs). Thus, for the great majority of patients, particularly for the elderly, the options are to continue TKI therapy life-long or to enter an intermittent TKI administration, as previously published ( Russo D et al, Blood 2013; Russo et al Blood Adv 2015). The probability of major molecular response (MMR or MR3.0) maintenance while on intermittent 1 month on/1 month off TKI at 1 year is 80%, as reported recently in the first interime analysis of the Italian prospective randomized OPTkIMA trial (Malagola M et al, Cancer Med 2021). This is the second interim report of OPTkIMA trial, in which elderly patients with Ph+ CML in sustained (≥ 2 years) confirmed major molecular response (MMR or MR3.0) or deep molecular response (MR4.0 or deeper) were randomly assigned to receive a FIXED intermittent schedule (1 month on/1 month off) vs a PROGRESSIVE intermittent schedule (1 month on/1 month off for the 1 st year, 1 month on/2 months off for the 2 nd year, 1 month on/3 months off for the 3 rd year). After the 3 rd year, clinicians were free to decide if maintain the intermittent schedule, discontinue TKI or resume TKI daily ( Malagola M et al, Cancer Med 2021). At last follow up, 203 patients are evaluable after randomization (104 FIXED vs 99 PROGRESSIVE). At 3 rd year (end of study protocol), by intention to treat, 28/104 (27%) and 45/99 (45%) patients discontinued OPTkIMA because of MR3.0 loss in the FIXED vs PROGRESSIVE arm, respectively (p=0.005). The percentages of patients who discontinued OPTkIMA because of MR3.0 loss at 1 st, 2 nd and 3 rd year in the FIXED vs PROGRESSIVE arm were: 24% in both arms (p=0.97), 1% vs 22% (p=0.001) and 3% vs 15% (p=0.01), respectively (Figure 1). The probability of survival without MR3.0 loss at 1, 2 and 3 years in the FIXED vs PROGRESSIVE arm were: 81%, 69% and 66% vs 81%, 59% and 53%, respectively (Figure 2; p=0.13). None of the patients who lost MR3.0 progressed to accelerated or blastic phase (AP/BP) and all of the patients regained the MR3.0 after continuous TKI resumption within 9 months. At the end of the 3 rd year from randomization, 61/104 (59%) and 36/99 (36%) patients were in MR3.0 or deeper response in the FIXED vs PROGRESSIVE arm, respectively (p=0.001). For these patients, comparing the two arms, Clinicians' choice was to maintain the ongoing intermittent schedule in 46% vs 28% of the cases (p=0.01), discontinue TKI with the goal of TFR in 36% vs 58% (p=0.03), and resume the TKI continuously in 18% vs 14% of the patients (p=0.59). The results of the OPTkIMA trial clearly confirm that a policy of intermittent TKI administration in elderly patients with Ph+ CML in MR3.0 or deeper response is safe, as no progression to AP/BP was observed. Furthermore, the great majority of protocol discontinuation for MR3.0 loss were recorded in the 1 st year (one month on and one month off in both arms). Then the cumulative incidence of patients who lost MR3.0 beyond the 1 st year was significantly higher in the PROGRESSIVE arm with a trend towards a higher probability of survival without MR3.0 loss in the FIXED arm (Figure 1). Finally, at the end of the study protocol (3 rd year), patients in MR3.0 or deeper response after a FIXED intermittent schedule were more likely addressed to maintain the same program, whereas patients included in the PROGRESSIVE arm were more frequently discontinued with the goal of TFR. This last observation represents a “real-life” CML management by Clinicians. It suggests that after a PROGRESSIVE intermittent therapy, patients were considered at high probability to safely maintain the TFR.

Introduction. Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) patients are commonly treated with tyrosine kinase inhibitors (TKI) in combination with either steroids, chemotherapy and more recently also immunotherapy. In the past, allogeneic transplant (SCT) was considered the only curative option; however, with the introduction of more potent TKIs as well as immunotherapy this milestone is nowadays debated, mostly for patients who achieve a molecular response. Moreover, as in chronic myeloid leukemia (CML), it is becoming relevant to understand if patients may over time discontinue TKI treatment. For this purpose, it is pivotal to report the outcome of Ph+ ALL patients who, for any reason, stopped TKI treatment. Patients and Methods. Forty-seven adult Ph+ ALL patients treated since 1 January 2000, and who did not undergo a SCT, were retrospectively collected from 12 Italian centers participating to the Campus ALL network. Their treatment plan included a TKI +/- chemotherapy according to the center current practice and/or according to the ongoing national trial they were enrolled in. The median age was 63 years (20-84), 20 patients (43%) were males, 30 patients harbored a p190 transcript, 15 a p210 transcript and 2 had both transcripts. Twenty-six patients were treated within a trial, while 21 were off-protocol. For 32 patients, induction was based only on a TKI plus steroids, whereas the remaining 15 received a combination of a TKI plus chemotherapy (in 3 cases high intensity protocols such as the NILG (Northern Italian Leukemia Group) and HCVAD regimens, in 12 low dose chemotherapy). The reasons not to transplant patients were: donor unavailability (5), clinical decision, mainly due to age/unfitness (30), patient's refusal (4), and achievement of a molecular response (i.e. at least BCR-ABL/ABL ≤0.01%) (8). The median follow-up was 60 months, with a median overall survival (OS) not reached at the last follow-up and a median disease-free survival (DFS) of 12 years. At the last follow-up, 12/47 patients had experienced a relapse. At the end of the induction (i.e. after 3 months, at a median of +82 days, from treatment initiation), 27 patients had achieved a molecular response. Overall. a molecular response was obtained in 40/46 pts (data not available for 1 case) after a median of 5 month, and was associated with a significantly lower hazard of disease recurrence (HR=0.057, 95% CI: 0.006-0.51, p=0.011) after adjusting for gender, fusion protein, association with chemotherapy, CMR at 3 months. Results. TKI treatment was discontinued in 14 of the 47 patients evaluated. The reasons for discontinuation were either toxicity (6) or clinical/patient decision (8). Eight patients harbored a p190 transcript, 5 a p210 transcript and 1 carried both. At the time of discontinuation, the median age was 75 years (23-87) and patients had been on a TKI for a median of 57.5 months (8-160) prior to stopping treatment. For these cases, the median WBC at diagnosis were 8.6 x 10 9/l (2.1-306 x 10 9/l). In 7 patients the first TKI used was imatinib, in 3 dasatinib, in 3 ponatinib and in 1 nilotinib. All patients but 1 had achieved a molecular response before stopping treatment; the only patient who never achieved a molecular response prior to discontinuing the TKI had a rapid relapse (1 month). At the last follow-up, 9 cases were still in treatment-free remission (TFR), whereas 5 eventually relapsed after 1, 1, 4, 14 and 30 months, respectively. Re-challenge with a TKI led to a hematological and molecular response in 3 of the 5 patients. The remaining 2 patients, who had been previously heavily treated and whose TFR was of only 1 month, received salvage standard chemotherapy but eventually died from ALL progression. The median time of TFR for the entire cohort of 14 patients was 20.5 months (1-82). When considering only the 9 patients who remain off treatment, the median time of TFR was 29.5 months (7-82) (Table 1, Figure 1). Conclusions. We report the outcome of 14 Ph+ ALL patients who discontinued TKI treatment due to various reasons. Nine of them are still on TFR after more than 2 years at the last follow-up, reinforcing the concept that a TFR is feasible in selected adult Ph+ ALL patients. Of further relevance, TKI re-challenge was successful in 3/5 patients who relapsed, similarly to what observed in CML.