Non-mucinous adenocarcinomas and squamous cell carcinomas of the anal region masquerading as abscess or fistula: a retrospective analysis and systematic review of literature.

PURPOSE: Abscess or fistula of the anal region is an uncommon presentation of malignancy. Under the assumption of a benign condition, diagnostics is often delayed, resulting in advanced tumour stages at first diagnosis. Due to the case rarity, treatment guidelines for cancers of anorectal region masquerading as abscess or fistula are missing. METHODS: We analysed all patients presenting with an abscess or fistula of the anal region in our department between January 2004 and August 2020. The malignancies were included to our study to acquire data on clinical presentation, treatment and outcome. Furthermore, a systematic review to present adenocarcinomas and squamous cell carcinomas associated to an abscess or fistula was performed. RESULTS: 0.5% of the patients treated for an abscess or fistula of the anal region met the selection criteria. Mean time from the onset of symptoms to diagnosis of malignancy was 100 days. Histology revealed adenocarcinoma and squamous cell carcinoma each in two patients. All patients had locally advanced tumours without distant metastases, in two cases with regional lymph-node metastases. Neoadjuvant chemoradiation was applied in two patients. All patients underwent abdomino-perineal resection of the rectum. The overall outcome reveals a recurrence-free survival of 4.5 and 3 years for two patients. Further two patients died within 5 months after the primary resection. CONCLUSION: Advanced carcinomas of the anorectal region may masquerade as abscess or fistula, cause diagnostic problems and delay oncologic treatment. However, even in these very advanced situations, surgical therapy with curative intent should be attempted.

Plants and Surgery: The Protective Effects of Thymoquinone on Hepatic Injury-A Systematic Review of In Vivo Studies.

Multimodal treatment concepts including liver transplantation for hepatocellular carcinoma (HCC), extended resection methods and neoadjuvant chemotherapy for colorectal liver metastasis significantly improve patients’ outcome. However, surgery-induced hepatic ischemia-reperfusion injury (IRI) and chemotherapy-associated hepatotoxicity result in hepatocellular damage and compromised liver function. Activation of common key pathways in ischemic liver and hepatotoxic injury results in oxidative stress, inflammatory responses and apoptosis causing organ damage. Controlling liver damage before and during surgery is essential for the postoperative outcome. Nigella sativa has a long tradition as a natural remedy. In the essential oil, Thymoquinone (TQ) was identified as the main component and responsible for most of the therapeutic effects. Therefore, this systematic review aimed to summarize the hepatoprotective effects of TQ and its potential suitability to improve surgical outcome by reducing surgical ischemic injury and hepatotoxicity of neoadjuvant chemotherapy. The key findings can be summarized as TQ having strong antioxidant, anti-inflammatory, antifibrotic, anti-/proapoptotic and anticarcinogenic effects. Almost no side effects were reported irrespective of a large dose range, suggesting a wide therapeutic window. These results give rise to the expectation that TQ could evolve to a novel powerful drug to reduce hepatic injury.

External validation of the 8th American Joint Committee on Cancer staging system for gall bladder carcinoma.

BACKGROUND: To validate the changes within the American Joint Committee on Cancer (AJCC) 8th staging system for gall bladder carcinoma compared to AJCC 7th staging system. METHODS: Surveillance, Epidemiology and End Results (SEER) database [2004-2014] was queried. Kaplan-Meier survival analyses and Log-rank testing were assessed according to both AJCC 7th and 8th staging systems. Likewise, Cox cancer-specific hazard ratio was evaluated according to both staging systems. RESULTS: Overall survival was assessed according to the two staging systems; and P values for overall trend (log/rank test) were significant (P<0.001) for both scenarios. Cox regression cancer-specific hazard adjusted for age, gender, histology, gender and surgery was evaluated according to the two staging systems. According to AJCC 7th staging system, the following pair wise hazard ratio comparisons were significant (II vs. IIIA; IIIB vs. IVA; IVA vs. IVB). According to AJCC 8th staging system, the following pair wise hazard ratio comparisons were significant (II vs. IIIA; IVA vs. IVB). C-statistic was assessed using death from gall bladder carcinoma as the dependent variable; and the findings for the two staging systems were as follows: AJCC 7th staging system: 0.684 (SE: 0.008; 95% CI: 0.667-0.701); AJCC 8th staging system: 0.682 (SE: 0.009; 95% CI: 0.665-0.698). CONCLUSIONS: There is a comparable discriminatory performance for AJCC 8th staging system compared to AJCC 7th staging system. Change form location-based to number-based N category assessment does not improve the overall prognostic performance of the staging system.

Immune-related musculoskeletal toxicities among cancer patients treated with immune checkpoint inhibitors: a systematic review.

AIM: Immune-related musculoskeletal toxicities are uncommon but potentially serious adverse events; and they may accompany the use of immune checkpoint inhibitors (ICIs). The objective of this systematic review is to assess the patterns of these musculoskeletal toxicities. METHODS & RESULTS: PubMed database has been searched till May 2017. Clinical studies and case reports reporting the occurrence of immune-related musculoskeletal toxicities (other than arthralgia and myalgia) in cancer patients treated with ICIs were included. Eight trials with 2263 participants were included. Likewise, nine case reports reporting the outcomes of 12 patients were included. CONCLUSION: Immune-related arthritis and myositis occur uncommonly in cancer patients treated with ICIs. Further studies are required to better describe the pathogenesis as well as the time course of these events.

Cigarette smoking as a risk factor for the development of and mortality from hepatocellular carcinoma: An updated systematic review of 81 epidemiological studies.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and its incidence has increased during the past decade. While hepatitis B and C virus infections and alcohol were established risk factors, the impact of smoking on the incidence and mortality of HCC was needed to be confirmed. METHODS: We reviewed cohort and case-control studies evaluating the association between cigarette smoking and incidence and mortality of HCC from MEDLINE and Google Scholar. We also checked reference lists of original studies and review articles manually for cross-references up to February 2016. We extracted the relevant information on participant characteristics and study outcomes, as well as information on the methodology of the studies. We also assessed the quality of the included trials using critical appraisal skills program checklists. Meta-analysis was performed by using RevMan 5.3 software. RESULTS: A total of 81 studies were included in the systematic review. Pooled OR for HCC development with current smokers was 1.55 (95% CI: 1.46 to 1.65; P < 0.00001). Pooled OR for HCC development with former smokers was 1.39 (95% CI: 1.26 to 1.52; P < 0.00001) and pooled OR for HCC development with heavy smokers was 1.90 (95% CI: 1.68 to 2.14; P < 0.00001). Pooled OR for the mortality of current smokers with HCC was 1.29 (95% CI: 1.23 to 1.34; P < 0.00001); and for former smokers with HCC, it was 1.20 (95% CI: 1.00 to 1.42; P = 0.04). CONCLUSIONS: Cigarette smoking increases the incidence and mortality of HCC. Further studies are needed to evaluate possible impact of quitting smoking on decreasing this risk.

Is Hepatic Resection for Non-colorectal, Non-neuroendocrine Liver Metastases Justified?

BACKGROUND: Discussions about the benefit of liver resection (LRx) for non-colorectal, non-neuroendocrine metastases are controversial. This study aimed to analyze the outcome of LRx for these patients and validate a previously published prognostic risk model. METHODS: The study analyzed 150 patients who underwent LRx for non-colorectal non-neuroendocrine (NCNN) metastases. Patients' demographics, tumor characteristics, treatment options, and postoperative outcome were investigated. The Kaplan-Meier method and Cox regression models were used to assess survival and prognostic variables. RESULTS: After a median follow-up period of 61 months, 39 % of the patients were alive. The 30-day mortality rate was 0.7 %. The overall, disease-free, and intrahepatic recurrence-free survival rates were respectively 42, 29, and 51 % at 5 years and 28, 23, and 47 % at 10 years. The negative prognostic factors identified in the multivariate analysis were melanoma (p = 0.04), squamous tumors (p = 0.01), and a primary tumor liver metastasis, with an interval shorter than 2 years (p = 0.02), whereas the predictive prognostic factors identified were breast cancer (p = 0.04), stromal tumors (p = 0.03), and major LRx (p = 0.04). The prognostic risk score stratified patients into low risk (0-3 points: n = 50; 5-year overall survival [OS] 58 %), medium risk (4-6 points: n = 91; 5-year OS 35 %), and high risk (≥7 points: n = 9; 5-year OS, 33 %) groups (p = 0.01). CONCLUSION: Liver resection for patients with NCNN metastases is a safe treatment option. More than 25 % of patients can achieve a long-term survival of 10 years when the histology of the primary tumor and the surrogates for the individual biologic tumor behavior are taken into account. Exclusion of patients with NCNN liver metastases from surgical therapy is no longer justified.

Navigated liver biopsy using a novel soft tissue navigation system versus CT-guided liver biopsy in a porcine model: a prospective randomized trial.

RATIONALE AND OBJECTIVES: The aim of this prospective, randomized animal study was to compare a new computer guided needle-based navigation system for liver biopsy with conventional computed tomography (CT)-guided liver biopsy. Computer-navigated interventions provide continuous needle tracking during motion and deformation from patient respiration and movement. MATERIALS AND METHODS: Twenty artificial tumors of about 5 mm in diameter were injected into the livers of five pigs, each at a different site. Each tumor was targeted by conventional CT-guided and computer navigated intervention. Intervention was considered complete after successful tumor biopsy. Data on procedure time, number of CT scans performed, accuracy, and success rate were recorded. RESULTS: All tumors (100%) were biopsied successfully. Mean procedural time was comparable between the two techniques (20 ± 9 minutes conventional versus 20 ± 8 minutes navigation). Mean number of CT scans were 1.2 ± 0.4 with navigation and 6.1 ± 3.8 with the conventional technique (P < .01). The dose-length product in the conventional group was significantly higher (212 ± 116 mGy × cm) than in the navigated group (78 ± 22 mGy × cm; P < .001). Mean number of capsule penetrations was 4 ± 1 with navigation versus 2 ± 1 with the conventional technique (P < .001). CONCLUSION: Computer-navigated liver biopsy may provide a promising and innovative device for easy, rapid, and successful liver biopsies with low morbidity. Further technical improvements and clinical studies in humans are required.

On combining internal and external fiducials for liver motion compensation.

This paper presents an in-vivo accuracy study on combining skin markers (external fiducials) and fiducial needles (internal fiducials) for motion compensation during liver interventions. We compared the target registration error (TRE) for different numbers of skin markers n(s) and fiducial needles n(f), as well as for different transformation types, in two swine using the tip of an additional tracked needle as the target. During continuous breathing, n(f) had the greatest effect on the accuracy, yielding mean root mean square (RMS) errors of 4.8 +/- 1.1 mm (n(f) = 0), 2.0 +/- 0.9 mm (n(f) = 1) and 1.7 +/- 0.8 mm (n(f) = 2) when averaged over multiple tool arrangements (n = 18, 36, 18) with n(s) = 4. These values correspond to error reductions of 11%, 64% and 70%, respectively, compared to the case when no motion compensation is performed, i.e., when the target position is assumed to be constant. At expiration, the mean RMS error ranged from 1.1 mm (n(f) = 0) to 0.8 mm (n(f) = 2), which is of the order of magnitude of the target displacement. Our study further indicates that the fiducial registration error (FRE) of a rigid transformation reflecting tissue motion generally correlates strongly with the TRE. Our findings could be used in practice to (1) decide on a suitable combination of fiducials for a given intervention, considering the trade-off between high accuracy and low invasiveness, and (2) provide an intra-interventional measure of confidence for the accuracy of the system based on the FRE.

In vivo accuracy assessment of a needle-based navigation system for CT-guided radiofrequency ablation of the liver.

Computed tomography (CT)-guided percutaneous radiofrequency ablation (RFA) has become a commonly used procedure in the treatment of liver tumors. One of the main challenges related to the method is the exact placement of the instrument within the lesion. To address this issue, a system was developed for computer-assisted needle placement which uses a set of fiducial needles to compensate for organ motion in real time. The purpose of this study was to assess the accuracy of the system in vivo. Two medical experts with experience in CT-guided interventions and two nonexperts used the navigation system to perform 32 needle insertions into contrasted agar nodules injected into the livers of two ventilated swine. Skin-to-target path planning and real-time needle guidance were based on preinterventional 1 mm CT data slices. The lesions were hit in 97% of all trials with a mean user error of 2.4 +/- 2.1 mm, a mean target registration error (TRE) of 2.1 +/- 1.1 mm, and a mean overall targeting error of 3.7 +/- 2.3 mm. The nonexperts achieved significantly better results than the experts with an overall error of 2.8 +/- 1.4 mm (n=16) compared to 4.5 +/- 2.7 mm (n=16). The mean time for performing four needle insertions based on one preinterventional planning CT was 57 +/- 19 min with a mean setup time of 27 min, which includes the steps fiducial insertion (24 +/- 15 min), planning CT acquisition (1 +/- 0 min), and registration (2 +/- 1 min). The mean time for path planning and targeting was 5 +/- 4 and 2 +/- 1 min, respectively. Apart from the fiducial insertion step, experts and nonexperts performed comparably fast. It is concluded that the system allows for accurate needle placement into hepatic tumors based on one planning CT and could thus enable considerable improvement to the clinical treatment standard for RFA procedures and other CT-guided interventions in the liver. To support clinical application of the method, optimization of individual system modules to reduce intervention time is proposed.