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The management of the primary tumor in metastatic colorectal, gastric and pancreatic cancer patients may be challenging. Indeed, primary tumor progression could be associated with severe symptoms, compromising the quality of life and the feasibility of effective systemic therapy, and might result in life-threatening complications. While retrospective series have suggested that surgery on the primary tumor may confer a survival advantage even in asymptomatic patients, randomized trials seem not to definitively support this hypothesis. We discuss the evidence for and against primary tumor resection for patients with metastatic gastrointestinal (colorectal, gastric and pancreatic) cancers treated with systemic therapies and put in context the pros and cons of the onco-surgical approach in the time of precision oncology. We also evaluate current ongoing trials on this topic, anticipating how these will influence both research and everyday practice.

Purpose: To compare the safety and efficiency of conventional monopolar and holmium laser en bloc transurethral resection of bladder tumor (CM-TURBT and HoL-EBRBT) while managing primary nonmuscle-invasive bladder cancer. Materials and Methods: From January 2012 to October 2015, fifty patients with primary nonmuscle-invasive bladder cancer underwent endoscopic surgery. Among them, 27 patients underwent CM-TURBT and 23 patients underwent HoL-EBRBT. Clinical data, included preoperative, operative, and postoperative management and follow-up, were recorded. Results: Patient demographics and tumor characteristics in both groups were compared before surgery. There was no significant difference in operative duration among the groups. Compared with the CM-TURBT group, HoL-EBRBT group had less intraoperative and postoperative complications, including obturator nerve reflex (P < 0.01), bladder perforation (P < 0.01), as well as bleeding and postoperative bladder irritation (P < 0.01). There were no significant differences among the two groups in the transfusion rate and occurrence of urethral strictures. Patients in the HoL-EBRBT group had less catheterization and hospitalization time than those in the CM-TURBT group (P < 0.01), and there were no significant differences in each risk subgroup as well as the overall recurrence rate among the CM-TURBT and HoL-EBRBT groups. Conclusions: HoL-EBRBT might prove to be preferable alternatives to CM-TURBT management of nonmuscle-invasive bladder cancer. HoL-EBRBT however did not demonstrate an obvious advantage over CM-TURBT in tumor recurrence rate.

The aim of this study was to compare the outcomes of four intraoperative monitoring approaches in order to compare their prognostic value in surgical complications of the facial nerve. This quasi-experimental study was conducted on 25 patients with Cerebellopontine Angle (CPA) tumors, who were hospitalized in the Valiasr Hospital, affiliated to the Arak University of Medical Sciences, Arak, Iran. The degree of the facial nerve paralysis was assessed based on the House-Brackmann (HB) facial nerve grading system. The Orbicularis oris and Oculi muscles were evaluated by electromyography (EMG) before and after the surgery. Monitoring the facial nerve was performed by the EMG, Facial Nerve Antidromic Potentials (FNAPs), Transcranial Electrical Stimulation (TES), and Brainstem Auditory Evoked Potentials (BAEPs) methods. The mean HB score was 0.36.6±5.83, indicating that the function of the facial muscle was abnormal in all the patients pre-surgery. The comparison of the four monitoring approaches six months after surgery showed that the predictive value of facial nerve TES was higher than the other approaches (P<0.005). Furthemroe, 4% of the patients showed normal function in the facial muscle after the surgery. In addition, 8%, 56%, and 32% of the patients had mild abnormalities, moderate to severe paralysis in the facial muscles, and severe facial nerve dysfunction, respectively. In summary, 36% of the patients showed a mild abnormalities in the follow-up period, and full recovery was observed in 28% of the cases. In conclusion, the transcranial motor evoked potential (TCMEP) is a useful method for monitoring the facial nerve during the surgery along with the continuous EMG recordings.

Surgical procedures such as tumor resection and biopsy are still the gold standard for diagnosis and (determination of) treatment of solid tumors, and are prognostically beneficial for patients. However, growing evidence suggests that even a minor surgical trauma can influence several (patho) physiological processes that might promote postoperative metastatic spread and tumor recurrence. Local effects include tumor seeding and a wound healing response that can promote tumor cell migration, proliferation, differentiation, extracellular matrix remodeling, angiogenesis and extravasation. In addition, local and systemic immunosuppression impairs antitumor immunity and contributes to tumor cell survival. Surgical manipulation of the tumor can result in cancer cell release into the circulation, thus increasing the chance of tumor cell dissemination. To prevent these undesired effects of surgical interventions, therapeutic strategies targeting immune response exacerbation or alteration have been proposed. This review summarizes the current literature regarding these local, systemic and secondary site effects of surgical interventions on tumor progression and dissemination, and discusses studies that aimed to identify potential therapeutic approaches to prevent these effects in order to further increase the clinical benefit from surgical procedures.

Background Solid tumors produce proteins that can induce the accumulation of bone marrow-derived cells in various tissues, and these cells can enhance metastatic tumor growth by several mechanisms. 4T1 murine mammary tumors are known to produce granulocyte colony-stimulating factor (G-CSF) and increase the numbers of immunosuppressive CD11b + Gr1 + myeloid-derived suppressor cells (MDSCs) in tissues such as the spleen and lungs of tumor-bearing mice. While surgical resection of primary tumors decreases MDSC levels in the spleen, the longevity and impact of MDSCs and other immune cells in the lungs after tumor resection have been less studied. Methods We used mass cytometry time of flight (CyTOF) and flow cytometry to quantify MDSCs in the spleen, peripheral blood, and lungs of mice bearing orthotopic murine mammary tumors. We also tested the effect of primary tumor resection and/or gemcitabine treatment on the levels of MDSCs, other immune suppressor and effector cells, and metastatic tumor cells in the lungs. Results We have found that, similar to mice with 4T1 tumors, mice bearing metastatic 4T07 tumors also exhibit accumulation of CD11b + Gr1 + MDSCs in the spleen and lungs, while tissues of mice with non-metastatic 67NR tumors do not contain MDSCs. Mice with orthotopically implanted 4T1 tumors have increased granulocytic (G-) MDSCs, monocytic (M-) MDSCs, macrophages, eosinophils, and NK cells in the lungs. Resection of primary 4T1 tumors decreases G-MDSCs, M-MDSCs, and macrophages in the lungs within 48 h, but significant numbers of functional immunosuppressive G-MDSCs persist in the lungs for 2 weeks after tumor resection, indicative of an environment that can promote metastatic tumor growth. The chemotherapeutic agent gemcitabine depletes G-MDSCs, M-MDSCs, macrophages, and eosinophils in the lungs of 4T1 tumor-bearing mice, and we found that treating mice with gemcitabine after primary tumor resection decreases residual G-MDSCs in the lungs and decreases subsequent metastatic growth. Conclusions Our data support the development of therapeutic strategies to target MDSCs and to monitor MDSC levels before and after primary tumor resection to enhance the effectiveness of immune-based therapies and improve the treatment of metastatic breast cancer in the clinic.

Bone sarcomas are rare primary malignant mesenchymal bone tumors. The three main entities are osteosarcoma, chondrosarcoma, and Ewing sarcoma. While prognosis has improved for affected patients over the past decades, bone sarcomas are still critical conditions that require an interdisciplinary diagnostic and therapeutic approach. While radiotherapy plays a role especially in Ewing sarcoma and chemotherapy in Ewing sarcoma and osteosarcoma, surgery remains the main pillar of treatment in all three entities. After complete tumor resection, the created bone defects need to be reconstructed. Possible strategies are implantation of allografts or autografts including vascularized bone grafts (e.g., of the fibula). Around the knee joint, rotationplasty can be performed or, as an alternative, the implantation of (expandable) megaprostheses can be performed. Challenges still associated with the implantation of foreign materials are aseptic loosening and infection. Future improvements may come with advances in 3D printing of individualized resection blades/implants, thus also securing safe tumor resection margins while at the same time shortening the required surgical time. Faster osseointegration and lower infection rates may possibly be achieved through more elaborate implant surface structures.

Purpose Preoperative risk stratification for patients undergoing metastatic brain tumor resection (MBTR) is based on established tumor-, patient-, and disease-specific risk factors for outcome prognostication. Frailty, or decreased baseline physiologic reserve, is a demonstrated independent risk factor for adverse outcomes following MBTR. The present study sought to assess the impact of frailty, measured by the Risk Analysis Index (RAI), on MBTR outcomes. Methods All MBTR were queried from the National Inpatient Sample (NIS) from 2019 to 2020 using diagnosis and procedural codes. The relationship between preoperative RAI frailty score and our primary outcome – non-home discharge (NHD) – and secondary outcomes – complication rates, extended length of stay (eLOS), and mortality – were analyzed via univariate and multivariable analyses. Discriminatory accuracy was tested by computation of concordance statistics in area under the receiver operating characteristic (AUROC) curve analysis. Results There were 20,185 MBTR patients from the NIS database from 2019 to 2020. Each patient’s frailty status was stratified by RAI score: 0–20 (robust): 34%, 21–30 (normal): 35.1%, 31–40 (very frail): 13.9%, 41+ (severely frail): 16.8%. Compared to robust patients, severely frail patients demonstrated increased complication rates (12.2% vs. 6.8%, p < 0.001), eLOS (37.6% vs. 13.2%, p < 0.001), NHD (52.0% vs. 20.6%, p < 0.001), and mortality (9.9% vs. 4.1%, p < 0.001). AUROC curve analysis demonstrated good discriminatory accuracy of RAI-measured frailty in predicting NHD after MBTR (C-statistic = 0.67). Conclusion Increasing RAI-measured frailty status is significantly associated with increased complication rates, eLOS, NHD, and mortality following MBTR. Preoperative frailty assessment using the RAI may aid in preoperative surgical planning and risk stratification for patient selection.

Cysteine might scavenge free radicals and is a limiting substrate for the cellular synthesis of glutathione (GSH). We investigated the association of cysteine with oxidative stress and GSH-related antioxidant capacity in colorectal cancer (CRC) patients. Plasma samples were drawn from 66 patients 1 day before (pre-resection) and 4 weeks after resection (post-resection). Tumor and adjacent normal tissues were collected. We measured levels of plasma and tissue cysteine, homocysteine, oxidative stress indicators (malondialdehyde, MDA; advanced oxidation protein products, AOPP), GSH, and antioxidant enzyme activities. After tumor resection, patients had significantly higher levels of plasma cysteine, homocysteine, MDA, AOPP, and GSH-related antioxidant enzyme activities when compared with pre-resection. Levels of cysteine, homocysteine, AOPP and all antioxidant capacity indicators in tumor tissue were significantly higher than those levels in the adjacent normal tissue. Plasma cysteine levels measured at pre-resection were positively associated with MDA levels in the tumor and in the adjacent normal tissues. Cysteine levels in tumor and adjacent normal tissues were significantly associated with tissue levels of homocysteine, almost as indicators of oxidative stress and antioxidant capacities. Cysteine in the circulation was likely utilized to mediate GSH-related antioxidant capacity and further cope with increased oxidative stress in tumor and adjacent normal tissues.

BackgroundEndoscopic submucosal tunneling has evolved to allow endoscopic resection of subepithelial tumors of gastrointestinal tract without full-thickness perforation. This study aimed to investigate safety and efficacy of submucosal tunnel resection for these tumors.MethodPatients with subepithelial tumors (SET) located in esophagus, gastric cardia, lesser curvature, and antrum were recruited. The size of tumor was limited to < 40 mm. The procedures were performed under general anesthesia. A mucosal entrance was created 2 cm proximal to the SET after submucosal injection. Submucosal tunnel was then extended and the tumor was dissected and mobilized with intact overlying mucosa. After complete dissection, the tumors would be retrieved per orally and mucosal entrance closed by endoclips.ResultsFrom June 2012 to December 2016, 51 patients with subepithelial tumors received POET. 39 patients had SET in stomach, 11 located in esophagus, and 1 in duodenum. The mean operative time was 90.46 ± 46.49 min, while the mean size of the tumors was 20.71 ± 14.05 mm. The POET was converted to endoscopic full-thickness resection (EFTR) in three patients with gastric subepithelial tumors located at greater curvature. The overall complication rate was 4.0%, and there was no bleeding, mucosal dehiscence, or leakage. The time to resume diet was 1.7 days, while the average hospital stay was 3.2 ± 1.0 days. The mean follow-up period was 19 ± 16 months, and only 1 patient developed recurrence of leiomyoma.ConclusionPer oral endoscopic tumor resection is safe and effective treatment for esophageal and gastric SET located at cardia, lesser curvature, and antrum. Currently, POET for treatment of upper GI SET is limited by the size and location of the tumor.

Perihilar cholangiocarcinoma (Klatskin tumor) is one of the most challenging hepatobiliary cancers to treat due to its critical location and tendency to involve nearby vascular structures in the portal hepatic. A combined biliary and major liver resection is often required to achieve a complete oncological resection. Traditionally, Klatskin tumor resection is performed using an “open” approach until recently when the minimally invasive technique becomes popular due to its proven advantages. The laparoscopic technique had been reported; however, the majority of resections were types I and II without the need for ipsilateral hepatectomy. Inherent limitations of straight laparoscopic instruments result in significant technical difficulties in performing precise tissue dissection and vessel repair and creating a fine bilioenteric anastomosis. In this didactical video, we described our technique of type IIIB Klatskin tumor (B3-L perihilar cholangiocarcinoma) resection utilizing a robotic technology. The use of a robotic platform facilitates precise porta hepatic dissection, bleeding control, and creation of a fine bilioenteric anastomosis at the level of the hilar plate. We believe that the robotic platform provides an alternative method for resection of perihilar cholangiocarcinoma with excellent short-term outcomes.