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Gliomas of the brainstem represent a small percentage of central nervous system gliomas in adults. Due to the proximity of the tumor to critical structures, radical surgery is highly challenging and limited to selected cases. In addition, postoperative treatments, which become exclusive to non-operable patients, do not guarantee satisfactory disease control, making the progression of the disease inevitable. Currently, there is a lack of therapeutic options to control tumor growth after the diagnosis of recurrence. The rarity of these tumors, their distinct behavioral characteristics, and the limited availability of tumor tissue necessary for the development of prognostic and predictive biomarkers contribute to the absence of a standardized approach for treating recurrent brainstem gliomas. A salvage radiotherapy (RT) retreatment could represent a promising approach for recurrent brainstem gliomas. However, to date, it has been mainly evaluated in pediatric cases, with few experiences available to assess the most appropriate RT dose, safety, and clinical responses in adult patients. This comprehensive review aims to identify instances of adult patients with recurrent brainstem gliomas subjected to a secondary course of RT, with a specific focus on the analysis of treatment-related toxicity and outcomes. Through this investigation, we endeavor to contribute valuable insights into the viability and efficacy of salvage RT retreatment in managing recurrent brainstem gliomas in the adult population.

Purpose: Clinical evidence suggests an association between comorbidities and outcome in patients with glioblastoma (GBM). We hypothesised that the internal carotid artery (ICA) calcium score could represent a promising prognostic biomarker in a competing risk analysis in patients diagnosed with GBM. Methods: We validated the use of the ICA calcium score as a surrogate marker of the coronary calcium score in 32 patients with lung cancer. Subsequently, we assessed the impact of the ICA calcium score on overall survival in GBM patients treated with radio-chemotherapy. Results: We analysed 50 GBM patients. At the univariate analysis, methyl-guanine-methyltransferase gene (MGMT) promoter methylation ( p = 0.048), gross total tumour resection ( p = 0.017), and calcium score ( p = 0.011) were significant prognostic predictors in patients with GBM. These three variables also maintained statistical significance in the multivariate analysis. Conclusions: the ICA calcium score could be a promising prognostic biomarker in GBM patients.

Radiotherapy (RT) is performed in approximately 75% of patients with cancer, and its efficacy is often hampered by the low tolerance of the surrounding normal tissues. Recent advancements have demonstrated the potential to widen the therapeutic window using "very short" radiation treatment delivery (from a conventional dose rate between 0.5 Gy/min and 2 Gy/min to more than 40 Gy/s) causing a significant increase of normal tissue tolerance without varying the tumor effect. This phenomenon is called "FLASH Effect (FE)" and has been discovered by using electrons. Although several physical, dosimetric, and radiobiological aspects need to be clarified, current preclinical " in vivo " studies have reported a significant protective effect of FLASH RT on neurocognitive function, skin toxicity, lung fibrosis, and bowel injury. Therefore, the current radiobiological premises lay the foundation for groundbreaking potentials in clinical translation, which could be addressed to an initial application of Low Energy Electron FLASH (LEE) for the treatment of superficial tumors to a subsequent Very High Energy Electron FLASH (VHEE) for the treatment of deep tumors. Herein, we report a clinical investigational scenario that, if supported by preclinical studies, could be drawn in the near future., Competing Interests: FM received personal support for attending meetings from SIT-Sordina. FP received personal support for attending meetings from SIT-Sordina and from Thema Sinergie. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ursino, Gadducci, Giannini, Gonnelli, Fuentes, Di Martino and Paiar.)

Despite countless papers in the field of radioresistance, researchers are still far from clearly understanding the mechanisms triggered in glioblastoma. Cancer stem cells (CSC) are important to the growth and spread of cancer, according to many studies. In addition, more recently, it has been suggested that CSCs have an impact on glioblastoma patients' prognosis, tumor aggressiveness, and treatment outcomes. In reviewing this new area of biology, we will provide a summary of the most recent research on CSCs and their role in the response to radio-chemotherapy in GB. In this review, we will examine the radiosensitivity of stem cells. Moreover, we summarize the current knowledge of the biomarkers of stemness and evaluate their potential function in the study of radiosensitivity.

Aim: Stereotactic ablative radiotherapy (SABR) showed increasing survival in oligometastatic patients. Few studies actually depicted oligometastatic disease (OMD) evolution and which patient will remain disease-free and which will rapidly develop a polymetastatic disease (PMD) after SABR. Therefore, apart from the number of active metastases, there are no clues on which proven factor should be considered for prescribing local treatment in OMD. The study aims to identify predictive factors of polymetastatic evolution in lung oligometastatic colorectal cancer patients., Methods: This international Ethical Committee approved trial (Prot. Negrar 2019-ZT) involved 23 Centers and 450 lung oligometastatic patients. Primary end-point was time to the polymetastatic conversion (tPMC). Additionally, oligometastases number and cumulative gross tumor volume (cumGTV) were used as combined predictive factors of tPMC. Oligometastases number was stratified as 1, 2-3, and 4-5; cumGTV was dichotomized to the value of 10 cc., Results: The median tPMC in the overall population was 26 months. Population was classified in the following tPMC risk classes: low-risk (1-3 oligometastases and cumGTV ≤ 10 cc) with median tPMC of 35.1 months; intermediate-risk (1-3 oligometastases and cumGTV > 10 cc), with median tPMC of 13.9 months, and high-risk (4-5 oligometastases, any cumGTV) with median tPMC of 9.4 months (p = 0.000)., Conclusion: The present study identified predictive factors of polymetastatic evolution after SABR in lung oligometastatic colorectal cancer. The results demonstrated that the sole metastases number is not sufficient to define the OMD since patients defined oligometastatic from a numerical point of view might rapidly progress to PMD when the cumulative tumor volume is high. A tailored approach in SABR prescription should be pursued considering the expected disease evolution after SABR, with the aim to avoid unnecessary treatment and toxicity in those at high risk of polymetastatic spread, and maximize local treatment in those with a favorable disease evolution., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background: There is an unmet need for new biomarkers able to predict both the outcomes of up-front therapy and the compliance of elderly patients diagnosed with glioblastoma. For this purpose, temporal muscle thickness is a promising tool to be investigated., Methods: Data from 52 glioblastoma patients older than 65 years, treated with post-operative radio or radio-chemotherapy and referred to Pisa University Hospital, were retrieved. The thickness of temporal muscle (TMT) was divided into quartiles and correlated with overall survival (Our primary endpoint). Survival curves were calculated using Kaplan-Meier method, and log-rank test was used to evaluate the differences between curves., Results: Patients in the lower quartile of TMT, with TMT thinner than 7 mm, have survived longer; both univariate and multivariate analyses showed a statistically significant correlation between TMT and overall survival (P = 0.012 and P = 0.003, respectively)., Conclusion: Future prospective and more extensive studies focused on elderly glioblastoma patients are needed to confirm the role of TMT as prognostic value on OS and to help explaining this association., (© 2022. Italian Society of Medical Radiology.)

Objectives: The present study aims to investigate the role of the first magnetic resonances (MRI) following radio-chemotherapy (RT-CT) in patients diagnosed with high-grade glioma., Methods: We retrospectively recorded radiological evaluations following RT-CT, symptoms related to disease progression (avoiding any sign due to radiotherapy or chemotherapy) and the change of therapeutic strategy., Results: In March 2021, at data analysis, the data of 149 patients diagnosed with high-grade glioma and treated between May 2013 and July 2020 were retrieved for the present analysis. Two out of 122 (1.6%), 5 out of 106 (4.7%) and 8 out of 92 (8.6%) asymptomatic patients received the diagnosis of disease recurrence at the time of the first, second and third MRI, respectively. Otherwise, 16 out of 27 (59.2%), 16 out of 24 (66.6%) and 13 out of 16 (82.2%) symptomatic patients changed their therapy after the first, second and third MRI, respectively. Among patients that experienced radiological signs of distant progression, 10 out of 14 were symptomatic and changed their therapy., Conclusions: MRIs performed by 6 months after the end of RT-CT lead to change treatment strategy mostly in symptomatic patients., (© 2022. Italian Society of Medical Radiology.)

Background . Systemic immunity and inflammation indexes (SI) derived from blood cells have gained increasing attention in clinical oncology as potential biomarkers that are associated with survival. Materials and methods . We tested 12 different SI using blood tests from patients with isocitrate dehydrogenase 1 and 2 wild-type glioblastomas, treated with radio-chemotherapy. The primary endpoint was their overall survival. Results . A total of 77 patients, comprising 43 males and 34 females, with a median age of 64 years (age range 26-84), who were treated between October 2010 and July 2020, were included in the present analysis (approved by a local ethics committee). In the univariate Cox regression analysis, all the indexes except two showed a statistically significant impact on OS. In the multivariate Cox regression analysis, neutrophil × platelet × leukocyte/(lymphocyte × monocyte) (NPW/LM) and neutrophil × platelet × monocyte/lymphocyte (NPM/L) maintained their statistically significant impact value. Conclusions . This univariate analysis confirms the potential of systemic inflammation indexes in patients with glioblastoma, while the multivariate analysis verifies the prognostic value of NPW/LM and NPM/L.

The impact of different patterns of glioblastoma (GBM) recurrence has not yet been fully established in patients suitable for a second surgery. Through the present observational study carried out at Pisa University Hospital, we aimed to investigate how different patterns of GBM failure influence second surgery outcomes. Overall survival (OS) and post-recurrence survival (PRS) were assessed according to clinical characteristics, including pattern of recurrence, in a prospective cohort of recurrent GBM patients. Survival curves were calculated using the Kaplan-Meier method and the log-rank test was applied to evaluate the differences between curves. Patients with local recurrence had better OS than patients with non-local one, 24.1 versus 18.2 months, respectively [P = 0.015, HR = 1.856 (1.130-3.050)]. The second surgery conferred an advantage in OS respect to non-operated patients, however, this advantage was more evident in patients with local recurrence [P = 0.002 with HR 0.212 (95% CI 0.081-0.552) and P = 0.029 with HR = 0.522 (95% CI 0.291-0.936), respectively]. The recurrence pattern can influence the outcome of patients with recurrent GBM suitable for a second surgery., (© 2021. Belgian Neurological Society.)

Aim: Pancreatic adenocarcinoma is a life-threatening disease with a rising frequency and the fourth leading cause of cancer death. This review aimed to assess the impact of postoperative radiotherapy through a meta-analysis of prospective randomized studies., Materials and Methods: Six studies met the inclusion criteria and were analyzed to calculate the cumulative risk of death (hazard ratio) in patients affected by pancreatic cancer treated with or without radiotherapy. Higgins' index was used to determine heterogeneity in between-study variability and, subsequently, the random-effects model was applied according to DerSimonian and Laird., Results: Eight hundred and thirty-seven patients were analyzed (418 in the control arm and 419 in the treatment one), the hazard ratio for death after randomization was 0.92 (p=0.560, 95% confidence interval=0.70-1.22). When scrutinizing these studies, only one out of six showed a statistically significant benefit due to the addition of radiotherapy in the postoperative setting., Conclusion: We conclude that the use of adjuvant radiotherapy is not beneficial in treating all patients affected by pancreatic cancer but only for a subset of cases with potential residual local disease., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

This study reports the results of a monocentric prospective analysis conducted with the aim of evaluating the impact of XRCC1 rs25487, XRCC3 rs861539, XRCC3 rs1799794, RAD51 rs1801320 and GSTP-1 rs1695 single nucleotide polymorphisms (SNP) on patients with high-grade glioma treated with concomitant radio-chemotherapy. From October 2010 to August 2019, a total of 75 patients aged ≥18 years, with histological diagnosis of high-grade glioma, isocitrate dehydrogenase (IDH) 1/2 wild type and treated with radio-chemotherapy and sequential chemotherapy with temozolomide (TMZ) were prospectively recruited. The local ethic committee approved this study (Comitato Etico di Area Vasta Nord Ovest [CEAVNO]; protocol 3304/2011). After a median follow up of 25 months (range: 7-98 months), median progression-free survival (PFS) and overall survival (OS) were 11 months (CI95%: 8-14 months) and 18 months (CI95%: 15-21 months), respectively. In univariate and multivariate Cox regression analysis, a statistically significant association with PFS and OS was found with XRCC3 rs1799794 SNP. The study suggests that XRCC3 rs1799794 SNP can be associated with different PFS and OS in glioblastoma patients treated with radio-chemotherapy., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Infected vascular grafts are associated with very high rates of limb loss and mortality. "Classic" treatment has invariably included graft excision. Recent reports have suggested that a more conservative approach may be indicated in selected cases, leaving the graft in place and using an aggressive local treatment associated with appropriate intravenous antibiotics. The authors report their experience with two patients with infected prosthetic vascular grafts in the groin. They both had purulent drainage from the groin wound, with the graft exposed close to the femoral anastomosis. They were both treated successfully without graft removal, and both graft maintained patency, with a follow-up of 22 and 19 months.

A case of femoral hernia following repair of an inguinal hernia with the Shouldice method is presented. The authors discuss the pathogenesis, suggest the use of ultrasound for a precise preoperative diagnosis, and propose the "plug" technique of Lichtenstein as the method of choice for the repair. This method offers a minimally invasive approach, without disturbing the previous inguinal repair and it is very simple to perform.

The authors report a case of infected pseudoaneurysm of the brachial artery in a drug addict, treated with aneurysm excision and brachio-brachial bypass with inverted saphenous vein. They review the literature on the subject and management options.

The use of stapling devices has changed the practice of colorectal surgery. The authors report their experience with the "double stapling" technique introduced by Knight and Griffen in 1980 for the performance of low colorectal anastomosis. They treated 42 patients, with a mean age of 63.2 years. In 34 surgery was performed for rectal adenocarcinoma, while 8 patients were being reoperated on for closure of a colostomy after Hartmann's operation. In one patient a diverting colostomy was fashioned because of poor bowel cleansing, secondary to a stenosing rectal carcinoma. Mortality was nil. There were no clinical anastomotic leaks. There were 2 cases of late postoperative anastomotic stenosis that responded to endoscopic pneumatic dilatation.

The authors report their experience with the treatment of endorectal foreign bodies (EFB). They review the literature on the subject and examine the various therapeutic options. Considering the possible complications of leaving an EFG in place for prolonged period of times in the hope of spontaneous delivery, they suggest that immediate removal is always indicated. They describe various technical modalities for endoscopic removal, that can avoid laparotomy in the majority of cases.

The authors report on a case of hepatic vein thrombosis or Budd-Chiari syndrome (BCS) successfully treated with recombinant Tissue Plasminogen Activator (rTPA). They briefly outline the etiology and symptomatology of this disease as well as the various surgical procedures used for treatment. Medical therapy has been so far poorly effective in treatment BCS, but recently various reports seem to indicate that rTPA may have a role. The authors suggest that rTPA may be used as the only therapy in selected cases, or in treating patients that are not candidates for surgical intervention, or as a temporizing measure to improve symptoms in patients awaiting surgery.

The authors report on three cases of cystic duct syndrome, a fairly uncommon complication of cholelithiasis, consisting in migration of a large gallstone from the gallbladder to the common bile duct, resulting in the formation of a common cavity between cystic, hepatic and common bile ducts. They review the pathogenesis of this entity, as well as the diagnostic modalities best suited to a precise diagnosis. They stress that surgical therapy must be chosen on a case by case basis, trying to restore a functional extrahepatic biliary tree.

The authors report a case of Caroli's disease associated with cholangiocarcinoma. The patient presented with pain and jaundice and ultrasonography disclosed multiple common bile duct stones, cystic dilatation of the extrahepatic biliary tree and a mass in the right lobe of the liver. At operation, after a frozen section demonstrated cholangiocarcinoma, a common bile duct exploration, right hepatic lobectomy and hepato-jejunostomy were performed. They review the literature on the subject and stress the fact that hepatic tumors are associated with Caroli's disease in 7% of cases. Therefore, in these patients, when a stenosis of the biliary tree is found, multiple diagnostic manoeuvres are indicated in order to exclude the presence of malignancy.

The authors report their experience in thirteen cases of mesenteric infarction. They emphasize the difficulty in diagnosing and treating this entity, considering also the impossibility in most centers of performing emergency selective angiography of the superior mesenteric artery (SMA) When feasible, mesenteric rivascularization should always be attempted, followed 24 hours later by a "second look" procedure.

After an introduction on the various aetiological factors involved in toxic megacolon, its onset, medical treatment and indications to surgery, the paper describes personal experience with seven cases. The report highlights the importance of medical treatment which is recommended as the appropriate initial therapeutic approach. Then after a review of evolving surgical techniques, it is suggested , again on the basis of personal experience, that the surgical approach should be neither excessively aggressive (total proctocolectomy with permanent ileostomy) nor excessively conservative (multistoma decompression). According to this report, the operation of choice is currently subtotal colectomy plus ileostomy and sigmoidostomy which combine modest morbidity and mortality with the possibility of future reconstruction.

The Authors report two cases of splenectomy for trauma, followed by heterotopic autotransplantation of splenic tissue in omental pockets. A follow-up nuclear scan and ultrasonography showed function and growth of the splenic implants. The pertinent surgical literature is reviewed.

In a series of 954 laparotomies performed for suspected acute appendicitis 5 (0.5%) cecal carcinomas were encountered. When considering patients over 50 years of age only, the incidence of right sided colon carcinomas raised to 5%. The authors review the therapeutic options in order to optimize patients' survival.