High-Grade Chondrosarcoma of the Proximal Phalanx: an Unusual Case of a Rare Entity.

Chondrosarcoma of the hand is a rare disease, but is one of the more common malignancies of the hand. Biopsies and imaging are a fundamental step in determining correct diagnosis, grading and selection for best treatment. We describe the case of a 77-year-old male complaining of a painless swelling in the proximal phalanx of the third ray of left hand. A biopsy was performed and the histology revealed a G2 chondrosarcoma. The patient underwent III ray amputation with metacarpal bone disarticulation and sacrifice of the radial digit nerve of the fourth ray. Definitive histology revealed grade 3 CS. Eighteen months after surgery, the patient is apparently disease-free with a good functional and aesthetic outcome although with persistent paresthesia of the fourth ray. Although there is no agreement in the literature for the treatment of low-grade chondrosarcomas, wide resection or amputation can be considered the mainstay treatment for high-grade tumors. Key words: chondrosarcoma, proximal phalanx, ray amputation, surgical treatment, tumor hand.

Influence of COVID-19 Pandemic on Colorectal Cancer Presentation, Management and Outcome during the COVID-19 Pandemic.

The aim of the study was to investigate whether the COVID-19 pandemic and related measures had an influence on colorectal cancer (CRC) presentation, management, and outcomes; it was a retrospective monocentric study. CRC patients undergoing surgery during the COVID-19 pandemic (1 March 2020-28 February 2022) (group B) were compared with patients operated on in the previous two years (1 March 2018-29 February 2020) in the same unit (group A). The primary outcome was to investigate whether there were differences in concern regarding the stage at presentation, as a whole and after dividing groups based on cancer location (right colon cancer, left colon cancer, rectal cancer). Secondary outcomes included differences in the number of patients admitted from emergency departments and emergency surgeries between periods, and differences in the postoperative outcomes. A subanalysis within the pandemic group was conducted on the same outcomes, dividing the aforementioned group based on pandemic trends. Two hundred and eighty (280) were operated on during the study period: 147 in group A and 133 in group B. Stage at presentation was similar between groups; however, the subgroups analysis showed that in the pandemic group, the number of early-stage left colon cancer occurrences almost halves, yet not significantly. Emergency department referral was more common in group B (p-value: 0.003); in group B, they also had longer operations and there was a more frequent use of ostomy. No differences in the number of postoperative complications nor in the postoperative outcomes were found. Patients with CRC were more frequently referred through the emergency department during the COVID-19 pandemic and left-sided cancers appear to be generally diagnosed at a more advanced stage. Postoperative outcomes showed that high specialized colorectal units can deliver standard high-level treatment under high-pressure external conditions.

Wide resection for giant-cell tumor of the distal radius: which reconstruction? A systematic review of the literature and pooled analysis of 176 cases.

Giant-cell tumor (GCT) is often more aggressive when located in the distal radius, and wide resection is then the gold-standard. No single reconstruction protocol is recommended, and the technique depends upon the surgeon's preferences. The aim of the present review was to determine the recurrence rate of GTC of the distal radius after intralesional treatment, to assess the results, advantages and complications of the various surgical techniques, and to draw up a decision-tree for surgical indications. The review of literature was performed in the main healthcare databases, searching for studies that reported results of wide resection and reconstruction of distal radius GCT. Local recurrence rates, metastasis rates, reconstruction techniques and respective results and complications were evaluated and analyzed. Sixteen studies were selected, for a total population of 226 patients; 6.0% and 0.9% experienced local recurrence and lung metastasis, respectively. Arthroplasty with non-vascularized or vascularized ipsilateral fibula were the most common techniques and were associated with the highest satisfaction rates: 86.4% and 88.0%, respectively. Arthroplasty with allograft presented a MusculoSkeletal Tumor Society (MSTS) score of 79.2% and arthroplasty with custom-made prosthesis presented an MSTS score of 81.8%. Arthrodesis was performed in 46 cases, with an MSTS score of 82.7%. Arthroplasty techniques are the most common in literature; they are used in patients who wish to conserve joint motion. Reconstruction with non-vascularized fibula seems to provide the best results, with lower morbidity. Arthrodesis is usually reserved for heavy manual workers or in case of arthroplasty failure.

Massive bone allograft engineered with autologous vessels: A new perspective for the future.

Reconstruction is very important to ensure good function and quality of life after bone tumor resection. For metacarpals and phalanges, amputation and toe transfer are the gold-standard indications; nevertheless, allograft reconstruction must also be taken into account. Unfortunately, because of its inert biological behavior, it undergoes progressive resorption, with frequent fracture. Several attempts have been made to induce new vascularization in massive bone allograft, with poor results. However, neo-angiogenesis was reported with vascular loops, and we therefore hypothesized that heterologous graft integration could be enhanced by creating a vascular loop through the graft. A 50-year-old male with chondrosarcoma of the ring finger of the left hand underwent wide resection. An allogenic middle phalanx of comparable size was then prepared to fill the defect. Two small windows were performed proximally and distally on the radial surface of the allogenic phalanx, and a 4 cm-long vein graft was inserted inside the medullary canal. Metacarpophalangeal joint stability was achieved by collateral ligament reconstruction with micro-anchors. The distal part of the allograft was then stabilized to the middle phalanx with a 1.5 mm-thick micro-plate and screws. The radial proper palmar digital artery was proximally and distally sutured end-to-end to the vein graft, under microscopy. At 12-month follow-up, the allograft was fused, and histology performed at plate removal at 18 months revealed viable spindle cells with osteoblastic differentiation, without evidence of atypia, in a dense fibrous stroma. At 22 months' follow-up, the patient was apparently disease-free, and satisfied with his manual function.

A novel local adipofascial flap for the management of recalcitrant ulnar tunnel syndrome.

Ulnar tunnel syndrome is the second most common upper-limb peripheral nerve compression syndrome. Recurrence or persistence of symptoms after primary surgery is found in 9.9%-21% of cases. The main cause of failure is peri- and endo-neural fibrosis, and management is difficult and controversial. Revision of nerve neurolysis combined with freestyle adipofascial flap provides nerve decompression and coverage with vascularized tissue, which prevents scar tissue formation around the nerve and restores glide. We performed a preliminary vessel-injected cadaver study. The perforating vessels from the posterior recurrent ulnar artery vascularize the medial adipose and fascial tissues of the elbow, allowing elevation of an adipofascial flap which is able to reach the ulnar nerve. Eight patients with neuropathic ulnar nerve pain in recalcitrant ulnar tunnel syndrome due to peri- and/or endo-neural fibrosis were treated by neurolysis, and the nerve was covered with an ulnar adipofascial flap. All patients were evaluated by percussion test, visual analog scale for pain, electromyography, electroneurography and ultrasound, and were classified according to the McGowan classification as modified by Goldberg. The study was approved by the review board. All patients had good 4-year outcome, with complete return to daily activity, work and sports 4 months after surgery. The results of this novel surgical technique were encouraging, without complications or donor site morbidity. Adipofascial flap combined with neurolysis could be a valid solution in the treatment of recalcitrant ulnar tunnel syndrome.

A systematic review and meta-analysis of PD-1/PD-L1 inhibitors in specific patient subgroups with advanced gastro-oesophageal junction and gastric adenocarcinoma.

BACKGROUND: immune checkpoint inhibitors(ICIs) have shown contradictory results in patients with advanced gastro-oesophageal junction/gastric cancer(GOJ/GC). AIM: to identify specific patient subgroups that would derive survival benefit from ICIs. METHODS: a subgroup meta-analysis of randomised clinical trials(RCTs) was carried out. RESULTS: four phase-III-RCTs were identified with data on the following variables: primary location(Gastric vs GOJ); age(≤ 65 vs >65); gender(male vs female); ECOG PS(0 vs 1); ethnicity (Asian vs non-Asian), histology(intestinal vs diffuse), PD-L1 expression(≥ 1% vs < 1%). PD-L1 positivity was significantly associated with survival benefit from ICIs (HR: 0.82, p 0.047), with a significant interaction between PD-L1 expression and ICI efficacy (interaction HR: 1.41, p 0.02). Numerically, the second most relevant interaction was ICI efficacy and gender, with ICI being more effective in males. CONCLUSION: The PD-L1 positive patient subgroup derives significant survival benefit from ICI in GOJ/GC, however other predictors are eagerly needed to further refine patient selection.

Histotype influences emergency presentation and prognosis in colon cancer surgery.

AIM: To investigate whether differences in histotype in colon cancer correlate with clinical presentation and if they might influence oncological outcomes and survival. METHODS: Data regarding colon cancer patients operated both electively or in emergency between 2009 and 2014 were retrospectively collected from a prospectively maintained database and analyzed for the purpose of this study. Rectal cancer was excluded from this analysis. Statistical univariate and multivariate analyses were performed to investigate possible significant variables influencing clinical presentation, as well as oncological outcomes and survival. RESULTS: Data from 219 patients undergoing colorectal resection for cancer of the colon only were retrieved. One hundred seventy-four patients had an elective procedure and forty-five had an emergency colectomy. Emergency presentation was more likely to occur in mucinous (p < 0.05) and signet ring cell (p < 0.01) tumors. No definitive differences in 5-year overall (44.7% vs. 60.6%, p = 0.078) and disease-free (51.2% vs. 64.4%, p = 0.09) survival were found between the two groups as a whole, but the T3 emergency patients showed worse prognosis than the elective (p < 0.03). Lymph node invasion, laparoscopy, histology, and blood transfusions were independent variables found to influence survival. Distribution assessed for pTNM stage showed T3 cancers were more common in emergency (p < 0.01). CONCLUSIONS AND DISCUSSION: Mucinous and signet ring cell tumors are related to emergency presentation, pT3 stage, poorest outcomes, and survival. Disease-free survival in patients who had emergency surgery for T3 colon cancer seems related to the histotype.

Biological and predictive role of ERCC1 polymorphisms in cancer.

Excision repair cross-complementation group 1 (ERCC1) is a key component in DNA repair mechanisms and may influence the tumor DNA-targeting effect of the chemotherapeutic agent oxaliplatin. Germline ERCC1 polymorphisms may alter the protein expression and published data on their predictive and prognostic value have so far been contradictory. In the present article we review available evidence on the clinical role and utility of ERCC1 polymorphisms and, in the absence of a 'perfect' trial, what we call the 'sliding doors' trial, we present the data of ERCC1 genotyping in our local patient population. We found a useful predictive value for oxaliplatin-induced risk of anemia.

New classification for the treatment of pyogenic spondylodiscitis: validation study on a population of 250 patients with a follow-up of 2 years.

PURPOSE: Pyogenic spondylodiscitis (PS) is still burdened by a high rate of orthopedic and neurological complications. Despite the rising incidence, the choice of a proper orthopedic treatment is often delayed by the lack of clinical data. The aim of this study was to propose a clinical-radiological classification of pyogenic spondylodiscitis to define a standard treatment algorithm. METHODS: Based on data from 250 patients treated from 2008 to 2015, a clinical-radiological classification of pyogenic spondylodiscitis was developed. According to primary classification criteria (bone destruction or segmental instability, epidural abscesses and neurological impairment), three main classes were identified. Subclasses were defined according to secondary criteria. PS without segmental instability or neurological impairment was treated conservatively. When significant bone loss or neurological impairment occurred, surgical stabilization and/or decompression were performed. All patients underwent clinical and radiological 2-year follow-up. RESULTS: Type A PS occurred in 84 patients, while 46 cases were classified as type B and 120 as type C. Average time of hospitalization was 51.94 days and overall healing rate was 92.80%. 140 patients (56.00%) were treated conservatively with average time of immobilization of 218.17 ± 9.89 days. Both VAS and SF-12 scores improved across time points in all classes. Residual chronic back pain occurred in 27 patients (10.80%). Overall observed mortality was 4.80%. CONCLUSIONS: Standardized treatment of PS is highly recommended to ensure patients a good quality of life. The proposed scheme includes all available orthopedic treatments and helps spine surgeons to significantly reduce complications and costs and to avoid overtreatment.

Estimating 12-week death probability in patients with refractory metastatic colorectal cancer: the Colon Life nomogram.

Background: Regorafenib and TAS-102 have recently demonstrated statistically significant survival gains in patients with refractory metastatic colorectal cancer (mCRC). Life expectancy ≥12 weeks was an inclusion criterion in registrative trials, and the identification of proper clinical selection tools for the daily use of these drugs in heavily pre-treated patients is needed to improve the cost-benefit ratio. We aimed at building a nomogram able to predict death probability within 12 weeks from the date of assessment of refractory mCRC. Patients and methods: Four hundred eleven refractory mCRC patients with ECOG performance status (PS) ≤2 receiving regorafenib, TAS-102 or other treatments were used as developing set. Putative prognostic variables were selected using a random forest model and included in a binary logistic model from which the nomogram was developed. The nomogram was externally validated and its performance was evaluated by examining calibration (how close predictions were to the actual outcome) and discriminative ability (Harrell C index) both on developing (internal validation) and validating (external validation) sets. Results: Four variables were selected and included in the nomogram: PS (P < 0.0001), primary tumor resection (P = 0.027), LDH value (P = 0.0001) and peritoneal involvement (P = 0.081). In the developing set, the nomogram discriminative ability was high (C = 0.778), and was confirmed in the validating set (C = 0.778), where the overall outcome was better as a consequence of the enrichment in patients receiving regorafenib or TAS-102 (46% versus 34%; P < 0.0001). Conclusions: Our nomogram may be a useful tool to predict the probability of death within 12 weeks in patients with refractory mCRC. Based on four easy-to-collect variables, the 'Colon Life' nomogram and free app for smartphones may improve mCRC patients' selection for later-line therapies and assist researchers for the enrollment in clinical trials in this setting.

Pregnancy-associated osteoporosis (PAO) with multiple vertebral fragility fractures: diagnosis and treatment in a young primigravid woman.

PAO is an uncommon condition affecting pregnant women during last trimester or early post-delivery period; it is often asymptomatic or presents with pain related to some acute fragility fractures. The diagnosis is often delayed or missed, the etiology remains unknown and no guidelines about treatment have been published. We present one case of PAO in a 33-year-old primigravid woman presenting acute worsening back pain. Our patient was treated with a TLSO brace, oral 25 (OH)-vitamin D supplementation and Teriparatide for 6 months. A short review of the literature has been included and useful advice about how to suspect and diagnose this uncommon disease were given in order to recognize and treat such a debilitating and severe condition for young mothers as best as possible, based on the available scientific evidences.

The Best. First. Anti-EGFR before anti-VEGF, in the first-line treatment of RAS wild-type metastatic colorectal cancer: from bench to bedside.

BACKGROUND: Since 2013, informative trials exploring the optimal use of available biologic agents in the first-line setting of metastatic colorectal cancer (mCRC) have been presented. These trials have opened a stimulating debate on the biological effect that first-line therapies may have on subsequent lines of treatment even long after the first-line progression. MATERIALS AND METHODS: We reviewed available preclinical and clinical data on the effect of different sequences of the biological drugs approved for use in mCRC patients. The importance of molecular selection of patients based on RAS mutational status and toxicity and quality-of-life issues were also analyzed. RESULTS: Convincing evidence exists on the optimal therapeutic effect obtained by using anti-EGFR agents in first-line treatment before anti-VEGF agents. On the contrary, up-front anti-VEGF agents' use seems to determine biological changes that increase the risk of acquired resistance to subsequent EGFR inhibitors. This hypothesis is confirmed by the scarce evidence of EGFR inhibitor activity in second-line treatment. Such a therapeutic optimum is subject to a fine molecular selection based on RAS mutational status. CONCLUSION: There is accumulating evidence suggesting that, after precise and well-established molecular selection, anti-EGFR agents deliver their maximum efficacy in mCRC patients when given early in the treatment strategy. Their toxicity profile seems manageable under the supervision of experienced physicians. Large randomized trials prospectively confirming the impact of different sequencing strategies are eagerly awaited.

Kyphoplasty vs conservative treatment: a case-control study in 110 post-menopausal women population. Is kyphoplasty better than conservative treatment?

OBJECTIVE: Osteoporosis is a highly prevalent disease worldwide. Consequences of vertebral osteoporotic fractures include pain and progressive vertebral collapse resulting in spinal kyphosis, decreased quality of life, disability and mortality. Minimally invasive procedures represent an advance to the treatment of osteoporotic VCFs. Despite encouraging results reported by many authors, surgical intervention in an osteoporotic spine is fraught with difficulties. Advanced patients age and comorbidities are of great concern. PATIENTS AND METHODS: We designed a retrospective case-control study on 110 post-menopausal women consecutively visited at our institution. Study population was split in a surgical and a conservative cohort, according to the provided treatment. RESULTS: Kyphoplasty treated patients had lower back pain VAS scores at 1 month as compared with conservatively treated patients (p < 0.05). EQ5D validated questionnaire also showed a better quality of life at 1 month for surgically treated patients (p < 0.05). SF-12 scores showed greater improvements at 1 month and 3 months with statistically significant difference between the two groups just at 3 months (p < 0.05). At 12 months, scores from all scales were not statistically different between the two cohorts, although surgically treated patients showed better trends than conservatively treated patients in pain and quality of life. Kyphoplasty was able to restore more than 54.55% of the original segmental kyphosis, whereas patients in conservative cohort lost 6.67% of the original segmental kyphosis on average. CONCLUSIONS: Kyphoplasty is a modern minimal invasive surgery, allowing faster recovery than bracing treatment. It can avoid the deformity in kyphosis due to VCF. In fact, the risk to develop a new vertebral fracture after the first one is very high.

TNF-α gene promoter polymorphisms and risk of venous thromboembolism in gastrointestinal cancer patients undergoing chemotherapy.

BACKGROUND: TNF-α has been proposed as a predictive factor for venous thromboembolism (VTE). Genetic polymorphisms could regulate TNF-α production. However, the relationship between TNFA gene variants and VTE is not clarified. This study aims to investigate the predictive role of five different TNFA gene promoter SNPs, or their haplotype combination(s), for a first VTE episode in gastrointestinal cancer out-patients treated with chemotherapy. PATIENTS AND METHODS: Serum TNF-α levels and TNFA -863C/A, -857C/T, -376G/A, -308G/A and -238G/A gene promoter polymorphisms were retrospectively evaluated in 314 subjects, including 157 controls and 157 Caucasian patients with histologically diagnosed GI cancers beginning chemotherapy delivery (5-fluorouracil either as monotherapy or in combination with platinum compounds or irinotecan). RESULTS: Haplotype analysis showed that a five-loci haplotype (CTGGG haplotype) has higher frequency in GI cancer patients who developed VTE (n = 15) during chemotherapy [odds ratio = 2.7, 95% confidence interval (CI) 1.04-7.11, P = 0.04]. GI patients who remained VTE-free did not differ in CTGGG haplotype frequency from controls. No association was observed between serum TNF-α levels and TNFA haplotype, but both were independent predictors of VTE. Approximately 20% of GI cancer patients carrying the CTGGG haplotype developed VTE compared with 4% of the remaining 101 patients (hazard ratio = 5.6, 95% CI 1.8-17.6, P = 0.003). CONCLUSION: These results suggest that TNFA might represent a candidate gene contributing to VTE pathogenesis in GI cancer patients and suggest that VTE risk during chemotherapy might be genetically identified. Validation studies are needed for translation into clinical practice.

Nondestructive sampling of insect DNA from defensive secretion.

Nondestructive techniques to obtain DNA from organisms can further genetic analyses such as estimating genetic diversity, dispersal and lifetime fitness, without permanently removing individuals from the population or removing body parts. Possible DNA sources for insects include frass, exuviae, and wing and leg clippings. However, these are not feasible approaches for organisms that cannot be removed from their natural environment for long periods or when adverse effects of tissue removal must be avoided. This study evaluated the impacts and efficacy of extracting haemolymph from a defensive secretion to obtain DNA for amplification of microsatellites using a nondestructive technique. A secretion containing haemolymph was obtained from Bolitotherus cornutus (the forked fungus beetle) by perturbation of the defensive gland with a capillary tube. A laboratory experiment demonstrated that the sampling methodology had no impact on mortality, reproductive success or gland expression. To evaluate the quality of DNA obtained in natural samples, haemolymph was collected from 187 individuals in the field and successfully genotyped at nine microsatellite loci for 95.7% of samples. These results indicate that haemolymph-rich defensive secretions contain DNA and can be sampled without negative impacts on the health or fitness of individual insects.

Insulinemia and the risk of breast cancer and its relapse.

A fairly large body of evidence has shown that insulin is a tumour-promoting agent, especially for breast cancer. High circulating and microenvironmental levels of insulin may directly increase the risk of breast cancer via the activation of cognate receptors expressed on normal and cancer cells and indirectly be associated with other known metabolic risk factors of cancer that usually are present in conjunction with the hyperinsulinic state. The focus of this review is to analyse and discuss available data in the literature on the possible causative/prognostic role of insulin resistance/hyperinsulinemia in breast cancer development and progression.