Can Radiotherapy Empower the Host Immune System to Counterattack Neoplastic Cells? A Systematic Review on Tumor Microenvironment Radiomodulation

Despite the rising evidence in favor of immunotherapy (IT), the treatment of oncological patients affected by so-called “cold tumors” still represents an open issue. Cold tumors are characterized by an immunosuppressive (so-called cold) tumor microenvironment (TME), which favors host immune system suppression, cancer immune-escape, and a worse response to IT. However, the TME is not a static element, but dynamically mutates and can be changed. Radiotherapy (RT) can modulate a cold microenvironment, rendering it better at tumor killing by priming the quiescent host immune system, with a consequent increase in immunotherapy response. The combination of TME radiomodulation and IT could therefore be a strategy for those patients affected by cold tumors, with limited or no response to IT. Thus, this review aims to provide an easy, rapid, and practical overview of how RT could convert the cold TME and why cold tumor radiomodulation could represent an interesting strategy in combination with IT.     

Epidemiology of hip fractures in northwestern Italy: a multicentric regional study on incidence of hip fractures and their outcome at 3-year follow-up

Piedmont is a region in northwestern Italy counting 4.2 million inhabitants. The purpose of our study was to update data on incidence and outcomes of hip fractures (HF) in our region to present days. The data of all patients affected by HF in 2003 in Piedmont (total: 5,386 patients) were analyzed, determining the incidence of HF, mean age, sex, fracture pattern and treatment adopted. Additionally, 564 patients underwent a questionnaire on comorbidities, complications, functional outcome and survivorship. Overall incidence of HF was 126.13/100,000 inhabitants-year. Mean hospitalization was 13.67 days. Mean time to surgery was 2.67 days. Survivorship was 94% at 3-month, 71.32% at 1-year and 60.21% at 3-year follow-up. These up-to-date data on HF in our region are in accordance with the international literature and could prove useful for Orthopaedic and Trauma surgeons for giving information to patients and their relatives.     

Laparoscopic Medial-to-lateral Colon Dissection: How and Why

Laparoscopic colectomy is a difficult procedure with a long learning curve. We describe in this study our technique for right- and left-sided laparoscopic medial-to-lateral colectomy. The medial approach involves division of the vascular pedicle first, followed by mobilization of the mesentery toward the abdominal wall, and finally freeing of the colon along the white line of Toldt. This approach allows immediate identification of the plane between the mesocolon and the retroperitoneum and renders the dissection fast and safe. Our series of 50 consecutive laparoscopic colectomies supports this concept. We believe that surgeons familiar with this technique will have an important tool in their armamentarium to circumvent some of the challenges of laparoscopic colectomy.     

Colour Doppler and microbubble contrast agent ultrasonography do not improve cancer detection rate in transrectal systematic prostate biopsy sampling

Study Type – Diagnosis (RCT) Level of Evidence 1b What’s known on the subject? and What does the study add? Transrectal gray‐scale ultrasonography guided prostate biopsy sampling is the method for diagnosing prostate cancer (PC) in patients with an increased prostate specific antigen level and/or abnormal digital rectal examination. Several imaging strategies have been proposed to optimize the diagnostic value of biopsy sampling, although at the first biopsy nearly 10–30% of PC still remains undiagnosed. This study compares the PC detection rate when employing Colour Doppler ultransongraphy with or without the injection of SonoVue^TM microbubble contrast agent, versus the transrectal ultrasongraphy‐guided systematic biopsy sampling. The limited accuracy, sensitivity, specificity and the additional cost of using the contrast agent do not justify its routine application in PC detection.

OBJECTIVE

? To compare prostate cancer (PC) detection rate employing colour Doppler ultrasonography with or without SonoVue^TM contrast agent with transrectal ultrasonography‐guided systematic biopsy sampling.

PATIENTS AND METHODS

? A total of 300 patients with negative digital rectal examination and transrectal grey‐scale ultrasonography, with PSA values ranging between 2.5 and 9.9 ng/mL, were randomized into three groups: 100 patients (group A) underwent transrectal ultrasonography‐guided systematic bioptic sampling; 100 patients (group B) underwent colour Doppler ultrasonography, and 100 patients (group C) underwent colour Doppler ultrasonography before and during the injection of SonoVue^TM. ? Contrast‐enhanced targeted biopsies were sampled into hypervascularized areas of peripheral, transitional, apical or anterior prostate zones. ? All the patients included in Groups B and C underwent a further 13 systematic prostate biopsies. The cancer detection rate was calculated for each group.

RESULTS

? In 88 (29.3%) patients a histological diagnosis of PC was made, whereas 22 (7.4%) patients were diagnosed with high‐grade prostatic intraepithelial neoplasia or atypical small acinar proliferation. ? No significant differences were found among the three groups for cancer detection rate (P= 0.329). ? Additionally, low sensitivity, specificity and accuracy of colour Doppler with or without SonoVue^TM contrast agent were found.

CONCLUSIONS

? Prostate cancer detection rate does not significantly improve with the use of colour Doppler ultrasonography with or without SonoVue^TM. ? Although no collateral effects have been highlighted, the combined use of colour Doppler ultrasonography and SonoVue^TM determines adjunctive costs and increases the mean time for taking a single prostate biopsy.     

Tissue expansion of free and pedicled flaps after transfer: possibilities and indications

Tissue expansion in combination with flap transfer has been widely reported as preexpansion of flaps, but only once as expansion of a free flap after transfer. Three free flaps and one pedicled flap were expanded after transfer. Indication, timing of expander implantation and explantation, technical aspects, and complications are reviewed. Indications for expander implantation after flap coverage were adjacent scar contracture, a secondary ulcer, or correction of contour deformity. The expander was placed as early as 4.5 months after free flap transfer. Low grade infection and seroma were complications necessitating early expander removal in two cases. The outcome was satisfactory in all four patients. Tissue expansion after flap transfer has been shown to be a reliable reconstructive option in selected cases. Indications are rare and include hypertrophic scar formation, scar contracture, secondary ulceration, or reconstructive procedures. In early free flap expansion, it is critical to avoid mechanical pressure of the pedicle. In musculocutaneous flaps, this can be accomplished by placing the expander subcutaneously. If more than 6 months have passed since transfer of the flap, the randomized blood supply is sufficient to place the expander anywhere under the flap.     

<Superscript>18</Superscript>F-FDG PET/CT in sarcoidosis management: review and report of 20 cases

PURPOSE: To evaluate the interest of (18)F-fluoro-2-deoxy-D: -glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) for diagnosis and therapeutic follow-up of patients with sarcoidosis. METHODS: Twenty consecutive patients with biopsy-proven sarcoidosis were retrospectively included, in particular, 13 and seven cases of thoracic and extra-thoracic sarcoidosis, respectively. All patients underwent (18)F-FDG PET/CT, and 12 of them also (67)Ga scintigraphy. Five patients were re-examined by (18)F-FDG PET/CT to assess response to corticosteroid (CS) treatment. RESULTS: Sensitivity of (18)F-FDG PET/CT in detecting active sarcoidosis localizations was determined considering only biopsy-proven sites. For thoracic, sinonasal, and pharyngo-laryngeal localizations, (18)F-FDG PET/CT sensitivity was 100%, 100%, and 80%, respectively. Overall sensitivity for all 36 biopsy-proven localizations improved from 78% to 87% after excluding skin involvement. Considering only the 12 patients who underwent both scintigraphic examinations, overall sensitivity of (67)Ga scintigraphy and (18)F-FDG PET/CT was 58% and 79%, respectively and improved to 67% and 86% after excluding all sites of skin involvement. To evaluate the efficacy of CS treatment, five enrolled patients underwent second (18)F-FDG PET/CT. Complete regression of all foci of pathological tracer uptake was showed in two cases, permitting CS withdrawal after 2 and 6 months. Improvement but incomplete regression of mediastino-pulmonary disease occurred in two patients treated with CS for 19 and 21 months. Disease progression was assessed in one patient treated with decreasing doses of CS during 16 months. CONCLUSION: (18)F-FDG PET/CT allows to obtain a complete morpho-functional cartography of inflammatory active localizations and to follow treatment efficacy in patients with sarcoidosis, particularly in atypical, complex, and multisystemic forms.     

The sentinel node biopsy in early gastric cancer: a preliminary study

Background and aims Sentinel node biopsy is currently used in surgery of malignant melanoma and breast cancer. The feasibility of sentinel node mapping in gastrointestinal cancers and its diagnostic sensitivity is unclear. It could be of particular value in the management of early gastric cancer in which radical D2 lymphadenectomy may be unnecessary. Materials and methods From January 2004 to June 2005, ten patients with preoperative diagnosis of early gastric cancer and no nodal involvement (cT1N0) were submitted to sentinel node biopsy using the dual mapping procedure with endoscopic blue dye and ^99mTc radio colloid injection. All the patients underwent standard radical gastrectomy and D2 lymphadenectomy. The resected nodes were evaluated by routine (hematoxylin–eosin) histopathological examination; the sentinel (blue or hot) nodes, in addition, were evaluated with immunohistochemistry for cytokeratin. Results The detection rate of this procedure was 100%. The preliminary results and perspectives for feasibility of sentinel node biopsy and its accuracy in predicting the nodal status in early gastric cancer are discussed.     

The Role of Minimally Invasive Surgery in the Treatment of Lung Metastases

Introduction: The ideal surgical approach for pulmonary metastasectomy remains controversial. Thoracoscopic surgery may offer advantages in quality of life outcomes, with equivalent oncologic long-term results. This study aimed to demonstrate the validity of video-assisted thoracoscopic surgery (VATS) in the treatment of lung metastases. Methods: In all 224 patients who underwent 300 VATS metastasectomies from January 2000 to December 2013 were retrospectively reviewed. Sixty-nine patients underwent major resection (68 thoracoscopic lobectomies and one pneumonectomy) and 155 patients underwent a wedge resection/segmentectomy. Complete curative pulmonary resections were performed in 219 (97%) cases. The Kaplan–Meier method was used to estimate survival curves. Univariate and subsequent multivariate Cox model regression were performed to identify independent factors of overall survival. Results: One hundred eighty-six patients developed lung metastases from epithelial tumors, 28 from sarcomas, seven from melanomas, and three from germ cell tumors. The final pathological examination revealed no cases of R1 disease. After a mean follow-up of 40 months, 118 patients (53%) had died. According to a multivariate analysis, a better prognosis was not observed for patients with a particular histological type; in addition, disease-free interval time, age, number of metastases, and type of surgery did not have any statistical influence on long-term survival. Conclusions: Thoracoscopic surgery is a safe and efficacious procedure, with a five-year overall survival that is equivalent to open surgery.     

Recurrences, testicular growth and semen parameters after laparoscopic Palomo varicocelectomy

The aim of this study was to evaluate the influence of laparoscopic Palomo varicocelectomy on testicular volume and sperm parameters. Laparoscopic Palomo varicocelectomy was performed on 91 patients for left-sided grade II and grade III varicoceles. Ultrasound-derived testicular volumes, semen volume, sperm concentration, percentage sperm motility and total motile sperm count were compared before and after the procedure. Postoperative complications and recurrence rate were also assessed. There were no surgical complications. Four patients (5%) had a mild hydrocele, but did not need hydrocelectomy. No patients presented signs of testicular atrophy and the left testicular volume increased in the adolescents (p < 0.05), but not in the adults. Our data suggest that laparoscopic high mass ligation of both the testicular artery and vein is a highly effective, reliable method for the treatment of varicocele. It is associated with very low complication and recurrence rates and with an objective improvement in fertility parameters.     

Quantitative evaluation of background parenchymal enhancement (BPE) on breast MRI. A feasibility study with a semi-automatic and automatic software compared to observer-based scores

Objective:

To evaluate quantitative measurements of background parenchymal enhancement (BPE) on breast MRI and compare them with observer-based scores.

Methods:

BPE of 48 patients (mean age: 48 years; age range: 36–66 years) referred to 3.0-T breast MRI between 2012 and 2014 was evaluated independently and blindly to each other by two radiologists. BPE was estimated qualitatively with the standard Breast Imaging Reporting and Data System (BI-RADS) scale and quantitatively with a semi-automatic and an automatic software interface. To assess intrareader agreement, MRIs were re-read after a 4-month interval by the same two readers. The Pearson correlation coefficient (r) and the Bland–Altman method were used to compare the methods used to estimate BPE. p-value <0.05 was considered significant.

Results:

The mean value of BPE with the semi-automatic software evaluated by each reader was 14% (range: 2–79%) for Reader 1 and 16% (range: 1–61%) for Reader 2 (p > 0.05). Mean values of BPE percentages for the automatic software were 17.5 ± 13.1 (p > 0.05 vs semi-automatic). The automatic software was unable to produce BPE values for 2 of 48 (4%) patients. With BI-RADS, interreader and intrareader values were κ = 0.70 [95% confidence interval (CI) 0.49–0.91] and κ = 0.69 (95% CI 0.46–0.93), respectively. With semi-automated software, interreader and intrareader values were κ = 0.81 (95% CI 0.59–0.99) and κ = 0.85 (95% CI 0.43–0.99), respectively. BI-RADS scores correlated with the automatic (r = 0.55, p < 0.001) and semi-automatic scores (r = 0.60, p < 0.001). Automatic scores correlated with the semi-automatic scores (r = 0.77, p < 0.001). The mean percentage difference between automatic and semi-automatic scores was 3.5% (95% CI 1.5–5.2).

Conclusion:

BPE quantitative evaluation is feasible with both semi-automatic and automatic software and correlates with radiologists'' estimation.

Advances in knowledge:

Computerized BPE quantitative evaluation is feasible with both semi-automatic and automatic software. Computerized BPE quantitative scores correlate with radiologists'' estimation.