Health-Related Quality of Life in Patients With Metastatic Colorectal Cancer Undergoing Systemic Therapy With or Without Maximal Tumor Debulking.

BACKGROUND: Maintaining a sufficient health-related quality of life (HRQoL) is important in the palliative treatment of patients with metastatic colorectal cancer (mCRC). The ORCHESTRA trial (ClinicalTrials.gov identifier: NCT01792934) is designed to prospectively evaluate overall survival benefit and impact on HRQoL of tumor debulking when added to first-line palliative systemic therapy in patients with multiorgan mCRC. In the present study, we report the HRQoL associated with this combination treatment compared with standard systemic therapy. METHODS: Patients included in the ORCHESTRA trial with clinical benefit after 3 or 4 cycles of first-line palliative systemic therapy with fluoropyrimidines and oxaliplatin with or without bevacizumab were randomly assigned to maximal tumor debulking followed by systemic therapy versus systemic therapy alone. Patients completed the EORTC Quality of Life Questionnaire-Core 30 and the Multidimensional Fatigue Inventory questionnaire at prespecified time points during treatment. Between-group differences in HRQoL over time were evaluated with linear mixed model analyses. A pattern mixture approach was applied to correct for missing questionnaires due to progressive disease. RESULTS: A total of 300 patients were randomized to the intervention arm (n=148) or the standard arm (n=152). No statistically significant or clinically relevant differences in HRQoL and fatigue were observed when tumor debulking was added to systemic therapy. In patients of both study arms, HRQoL after 1 year of treatment was not significantly different from HRQoL at the time of randomization. Patients in the intervention arm experienced serious adverse events (SAEs) twice as often as patients in the standard arm (P≤.001). CONCLUSIONS: Maximal tumor debulking in combination with palliative systemic therapy in patients with multiorgan mCRC was significantly associated with more SAEs resulting from local therapy but no difference in HRQoL compared with palliative systemic therapy alone. There is a remarkable lack of association between the occurrence of SAEs and impact on HRQoL.

Preemptive Delivery and Immediate Resection for Fetuses with High-Risk Sacrococcygeal Teratomas.

INTRODUCTION: Fetuses with "high-risk" sacrococcygeal teratoma (SCT) have a mortality rate of 40-50%. While fetal surgery may benefit select fetuses prior to 27 weeks' gestation, many fetuses die due to consequences of rapid tumor growth after 27 weeks. Here we report our experience applying "preemptive" delivery to fetuses who manifest signs of decompensation between 27 and 32 weeks. METHODS: A retrospective review of SCT fetuses delivered between 2010 and 2016 at ≤32 weeks' gestation was performed. Patients who decompensated prior to 27 weeks and were treated with fetal surgery or neonatal palliation were excluded. RESULTS: Forty-two SCT fetuses were evaluated, and 11 were preemptively delivered in response to impending fetal or maternal decompensation. Nine (81.8%) survived. One death was due to pulmonary hypoplasia in a neonate with significant intra-abdominal tumor burden, and the other was due to in utero tumor rupture. There were no deaths related to prematurity in this cohort. CONCLUSIONS: Many fetuses with SCT manifest signs of decompensation between 27 and 32 weeks. In the absence of fetal hydrops prior to 27 weeks or tumor rupture in utero, early delivery is associated with favorable outcomes. Our single-center experience supports a management algorithm change to incorporate "preemptive" delivery for selected cases.

Impact of right upper quadrant cytoreductive techniques with extensive liver mobilization on postoperative hepatic function and risk of liver failure in patients with advanced ovarian cancer.

OBJECTIVE: Evaluate postoperative hepatic-function in patients with advanced ovarian cancer (OC) who underwent extensive right upper-quadrant (RUQ) cytoreduction in primary, relapsed or interval settings. METHODS: We retrospectively reviewed all patients with OC who underwent liver resection, mobilization and/or diaphragmatic-stripping between 01/2013 and 12/2016. Postoperative liver enzyme function (LFTs), assessed by alanine transaminase (ALT), alkaline phosphatase (ALP) and bilirubin (Bil), was correlated with postoperative complications. RESULTS: 132 patients were identified. 81 patients (61%) underwent upfront, 25(19%) interval and 26(20%) secondary cytoreduction. The surgical procedures were right diaphragmatic peritoneal stripping (81/132;61%), full-thickness resection (42/132;32%), liver-capsule resection (85/132;64%), porta-hepatis tumor resection (11/132;8%) and partial hepatectomy (5/132;4%). 74%(98/132) of patients increased their LFTs postoperatively with a peak at 24-hours. Highest ALT median was 1.7-fold of upper normal limit (UNL), with the highest ALT value rising up to 28-fold UNL on the 1st postoperative day (PoD)(range 6-1792 IU/L). Median value of highest ALP was within normal, with the highest ALP value rising up to 4-fold UNL on PoD 5(range 22-512 IU/L). Median value of highest Bilirubin level was also within normal, with highest Bilirubin level rising up to 6-fold UNL on PoD 5(range: 2-120 µmol/L). Mean LFT-normalization time was 7 days (range: 3-14 days). No significant morbidity was directly linked to LFT deterioration, apart from one case (0.8%) of fatal fulminant hepatic-failure. CONCLUSION: RUQ-cytoreduction is almost always associated with a transient LFT-increase, with no significant clinical implications and spontaneous normalization within the first postoperative week. Due to the existing risk of fulminant liver failure, albeit rare and difficult to predict, postoperatively elevated LFTs should be monitored, until normalization. Large prospective studies are required to assess the predictive value of LFTs and other risk factors for postoperative hepatic failure in patients with OC undergoing extensive RUQ-cytoreduction.

Feasibility, safety and clinical outcomes of cardiophrenic lymph node resection in advanced ovarian cancer.

OBJECTIVES: Surgical resection of enlarged cardiophrenic lymph nodes (CPLNs) in primary treatment of advanced ovarian cancer has not been widely studied. We report on a cohort of patients undergoing CPLN resection during primary cytoreductive surgery (CRS), examining its feasibility, safety, and potential impact on clinical outcomes. METHODS: We identified all patients undergoing primary CRS/CPLN resection for Stages IIIB-IV high-grade epithelial ovarian cancer at our institution from 1/2001-12/2013. Clinical and pathological data were collected. Statistical tests were performed. RESULTS: 54 patients underwent CPLN resection. All had enlarged CPLNs on preoperative imaging. Median diameter of an enlarged CPLN: 1.3cm (range 0.6-2.9). Median patient age: 59y (range 41-74). 48 (88.9%) underwent transdiaphragmatic resection; 6 (11.1%) underwent video-assisted thoracic surgery. A median of 3 nodes (range 1-23) were resected. A median of 2 nodes (range 0-22) were positive for metastasis. 51/54 (94.4%) had positive nodes. 51 (94.4%) had chest tube placement; median time to removal: 4d (range 2-12). 44 (81.4%) had peritoneal carcinomatosis. 19 (35%) experienced major postoperative complications; 4 of these (7%) were surgery-related. Median time to adjuvant chemotherapy: 40d (range 19-205). All patients were optimally cytoreduced, 30 (55.6%) without visible residual disease. Median progression-free survival: 17.2mos (95% CI 12.6-21.8); median overall survival: 70.1mos (95% CI 51.2-89.0). CONCLUSIONS: Enlarged CPLNs can be identified on preoperative imaging and may indicate metastases. Resection can identify extra-abdominal disease, confirm Stage IV disease, obtain optimal cytoreduction. In the proper setting it is feasible, safe, and does not delay chemotherapy. In select patients, it may improve survival.

Invasive sclerosing epitheloid fibrosarcoma in the lumbar spine- A rare case report.

INTRODUCTION AND IMPORTANCE: Sclerosing epitheloid fibrosarcoma is a rare variant of low grade sarcoma with specific histologic and immunohistochemical features, and often associated with a poor prognosis. CLINICAL PRESENTATION: We report a case of a 35-year old male who presented with 2 year history of lower back pain, radiating to both lower limbs, weakness to both lower limbs and weight loss more than 5kgs in the past 6 months, no past history of trauma, drenching night sweats, no TB contact history, no incontinence and no any comorbidities. He reported no history of alcohol intake or cigarette smoking, no history of exposure to radiations or similar presentation to his family and no features suggestive of metastasis. On examination - he had maximum midline tenderness L3-S1, no gibbous, upper limbs neurologically intact and power 3/5 to both lower limbs, sensation intact. Computed tomography scan and magnetic resonance imaging revealed an ill-defined osteolytic mass spanning L3 to L5, vertebral plana of L4 and involvement of the left paraspinal muscles. The tumor extended to the extradural space and was also abutting on the distal great vessels. Our intervention entailed laminectomy, tumor debulking and posterior instrumental fusion of the spine. Histopathology findings were in keeping with an invasive sclerosing epitheloid fibrosarcoma. He had adjuvant chemotherapy with good outcome. DISCUSSION: This case was unique due to its lumbar column location, abutting the distal vessels and despite its low grade, it illustrates the malignant potential which responded well to adjuvant chemotherapy. CONCLUSION: Invasive SEF is an aggressive tumor that requires early diagnosis. Multi-modal treatment with surgical resection, adjuvant chemotherapy can improve patient survival and quality of life.

Echocardiography-Guided Radiofrequency Ablation for Cardiac Tumors.

Background: Patients with cardiac tumors may present challenges for surgical resection due to poor clinical condition. Echocardiography-guided transapical radiofrequency ablation for cardiac tumors (TARFACT) potentially offers a less invasive palliative therapy option. Objectives: This study aimed to evaluate the safety and efficacy of TARFACT. Methods: Five patients with cardiac tumors (mucinous liposarcoma, myocardial hypertrophy with inflammatory cell infiltration mass, fibrous tissue tumor hyperplasia, myocardial clear cell sarcoma, and cardiac rhabdomyoma) were included. All patients underwent TARFACT and were assessed with electrocardiogram, echocardiographic imaging, biochemical analysis, and pathological confirmation. Results: The median follow-up for all patients was 9 (range 4-12) months. Three surviving patients were alive at their last follow-up (9, 12, and 12 months, respectively), whereas 2 patients with late-stage tumors survived 6 months and 13 months after TARFACT, respectively. After TARFACT, all patients showed significant reductions in tumor size: the mean length decreased from 6.7 ± 2.0 cm to 4.7 ± 1.8 cm (P = 0.007); and the mean width decreased from 5.0 ± 2.1 cm to 2.5 ± 0.7 cm (P = 0.041). NYHA functional class also improved: median (IQR) decreased from 3.0 (1.5) to 2.0 (1.0) (P = 0.038), Peak E-wave on echocardiography showed a mean increase from 64.4 ± 15.7 cm/s to 76.6 ± 18.6 cm/s (P = 0.008), and NT-pro BNP levels had a median (IQR) reduction from 115.7 (252.1) pg/mL to 55.0 (121.6) pg/mL (P = 0.043). Conclusions: TARFACT is a novel palliative treatment option for cardiac tumors, reducing accessible tumors and improving clinical symptoms in a preliminary group of patients. (Cardiac Tumors Interventional [Radio Frequency/Laser Ablation] Therapy [CTIH]; NCT02815553).

Metastatic squamous cell carcinoma masquerading as acute retinal necrosis.

Purpose: To describe a case of retinal and optic nerve metastases masquerading as acute retinal necrosis secondary to primary squamous cell carcinoma of the lung. Observations: A 66-year-old male with a history of Stage IV lung cancer, actively on chemotherapy, presented with right eye vision loss, an afferent pupillary defect, and partial visual field deficiencies. Exam revealed vitritis, macula-involving infiltrative retinitis, optic neuritis, and vasculitis of the right eye. The patient was treated empirically for acute viral retinitis with intravitreal foscarnet and ganciclovir injections and oral acyclovir and trimethoprim-sulfamethoxazole. A diagnostic pars plana vitrectomy with vitreous biopsy, intravitreal antivirals and silicone oil fill was performed. The resulting cytology was positive for malignant squamous cell carcinoma. Conclusions and importance: We present a unique case of primary squamous cell carcinoma metastasizing to the retina and optic nerve which masqueraded as an acute viral retinitis. To date, there have not been any reported cases on Pubmed or Google Scholar at publication time of known squamous cell carcinoma metastases to the retina that demonstrated interval growth leading to emergent elevations in intraocular pressure (IOP). This case demonstrates the importance of considering metastasis when encountering an atypical acute retinal necrosis case, as well as bring awareness to the possibility that elevated IOP may be the first sign of interval metastases, despite surgical debulking, in cases involving known tumor metastases to the retina.

Radical prostatectomy findings in patients with locally aggressive Grade group 5 prostatic adenocarcinoma and negative limited or extended pelvic lymph node dissection.

Current management options for high-risk prostate cancer (PCa) patients include radical prostatectomy with lymph node dissection and other local or systemic therapeutic approaches. However, there is paucity of data in the pathology literature on the radical prostatectomy findings in patients with locally aggressive Grade group 5 PCa with negative limited or extended lymph node dissection. A search was made through our Urologic Pathology files and consults of the senior author for patients who had radical prostatectomy specimens with locally aggressive Grade group 5 PCa and limited or extended lymph node dissection from 2010 to 2022. Patients with lymph node metastasis were excluded. Clinicopathologic and follow up data were obtained. Forty-two patients were included in the study. Mean age was 64 years (range: 49-79 years). Forty-one (98 %) patients had PCa Gleason score 4 + 5 = 9 and 1 (2 %) patient had Gleason score 5 + 4 = 9. Extraprostatic extension and/or bladder neck invasion was present in 30 (71 %) patients and seminal vesicle invasion was present in 20 (48 %) patients, of which 10 (50 %) were bilateral. Extended lymph node dissection was performed in 18 patients with mean of 22 lymph nodes (range: 6-51 lymph nodes). Limited lymph node dissection was performed in 24 patients with mean of 7 lymph nodes (range: 2-25 lymph nodes). This study demonstrates that a subset of patients with very advanced/high grade PCa still benefit from radical prostatectomy/tumor debulking even in the setting of positive margins, and may not have lymph node metastasis.

Utility of bronchoscopic intra-tumoral alcohol injection to restore airway patency.

BACKGROUND: In cases of malignant airway obstruction, achieving airway patency using conventional bronchoscopic modalities can be challenging and may not be satisfactory. We aim to present our experience of using intra-tumoral alcohol injection (ITAI) to help achieve airway patency in malignant airway obstruction. METHODS: A retrospective study of adult patients presenting with malignant airway obstruction who underwent bronchoscopy with ITAI at a university center between 2015 and 2020 was conducted. We present procedural and patients' characteristics along with any additional bronchoscopic or systemic interventions received. Patients were classified based on airway patency response (assessed qualitatively by an interventional pulmonologist) into those with good response (≥50% improvement in airway patency) vs. those with low response (<50% improvement in airway patency). RESULTS: Forty-two patients underwent ITAI, of which 34 (81%) had at least two bronchoscopies to evaluate response. The patient median age was 65.5 [interquartile range (IQR) 57.8-72]. Most patients had stage IV malignancy at the time of the bronchoscopy (57.1%) and had Eastern Cooperative Oncology Group (ECOG) performance status score of between 2-3. Eighty-two percent of the patients achieved good airway patency response at the conclusion of the procedures. The procedures were generally well-tolerated and only one patient had significant bleeding that was not directly related to ITAI and required intensive care unit monitoring for 24 hours after the procedure. CONCLUSIONS: Dehydrated alcohol is readily available, inexpensive and a safe drug that can be potentially injected directly in malignant airway obstructive lesions in a multimodality approach to achieve airway patency when traditional modalities reach their limitation. Further studies are warranted to determine whether ITAI is superior to other interventional methods, explore its utilization to treat peripheral malignant tumors, as well as to standardize the treatment protocol and determine the effects of ITAI on patient symptoms and quality of life.

Metabolic active peritoneal sites affect tumor debulking in ovarian and peritoneal cancers.

RATIONALE AND OBJECTIVES: To evaluate the impact of metabolic parameters in the peritoneal cavity on the likelihood of achieving complete tumor debulking in patients with ovarian and peritoneal cancers. MATERIALS AND METHODS: Forty-nine patients with ovarian and peritoneal cancers were included, who underwent pre-operative 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT). The immediate surgical outcome was dichotomized into complete and incomplete tumor debulking. 18F-FDG PET/CT was qualitatively and quantitatively assessed by scrutinizing 15 anatomical sites for the presence of peritoneal carcinomatosis (PC). Patient-based and site-based diagnostic characteristics were described. Metabolic parameters (SUVmax, metabolic tumor volume and total lesion glycolysis) and the number of 18F-FDG avid peritoneal sites were evaluated between the two groups. Receiver operating curve (ROC) analysis was performed to determine the optimal cut-off value in predicting incomplete tumor debulking. RESULTS: Twenty-seven out of the 49 patients had PC and 11 had incomplete debulking. Patient-based and site-based accuracies for detection of PC were 87.8 and 97.6%, respectively. The number of 18F-FDG avid peritoneal sites was significantly different between complete and incomplete debulking groups (0.6 ± 0.8 versus 2.3 ± 1.7 sites respectively, p = 0.001), and the only independent significant risk factor among other metabolic parameters tested (odd ratio = 2.983, 95% CI 1.104-8.062) for incomplete tumor debulking with an optimal cut-off value of ≥4 (AUC = 0.816). CONCLUSION: The number of 18F-FDG avid peritoneal sites increased the risk of incomplete tumor debulking after surgery and potentially useful in assisting treatment stratification in patients with ovarian and peritoneal cancers.

Fetal Surgery.

Fetal surgery is an established but still rapidly evolving specialty, born from the rationale that destructive embryologic processes, recognized early in gestation, can be curtailed by prenatal correction. As more and more centers begin offering fetal interventions, quality of care must be verified through transparency about clinical capabilities and resources. Level designations should be assigned based on capability, as in trauma and neonatal ICU centers for excellence, and volume requirements must be set for fetal surgery certification. Regionalization of this specialty care may be required to optimize outcomes.

Effect of surgical decompression of spinal metastases in acute treatment - Predictors of neurological outcome.

OBJECTIVE: Space-occupying spinal metastases (SM), commonly diagnosed because of acute neurological deterioration, consequently lead to immediate decompression with tumor removal or debulking. In this study, we analyzed a series of patients with surgically treated spinal metastases and explicitly sought to determine individual predictors of functional outcome. PATIENTS AND METHODS: 94 patients (26 women, 68 men; mean age 64.0 years) with spinal metastases, who had been surgically treated at our department, were included retrospectively. We reviewed the pre- and postoperative charts, surgical reports, radiographic data for demographics, duration of symptoms, histopathology, stage of systemic disease, co-morbidities, radiographic extension, surgical strategy, neurological performance (Frankel Grade Classification), and the Karnofsky Performance Index (KPI). RESULTS: Emergency surgery within <24 h after discharge had been conducted in 33% of patients. Prostate carcinoma (29.5%) and breast carcinoma (11.6%) were the most common histopathologies. Median KPI was 60% at admission that had significantly improved at discharge (KPI 70%; p = 0.01). The rate of complications without revision was 4.3%, the revision rate 4.2%. From admission to discharge, pain had been significantly reduced (p = 0.019) and motor deficits significantly improved (p = 0.003). KPI had been significantly improved during in-hospital treatment (median 60 vs 70, p = 0.010). In the multivariable analysis, predictors of poor outcome (KPI < 70) were male sex, multiple metastases, and pre-existing bowel and bladder dysfunction. Median follow up was 2 months. DISCUSSION: In our series, surgery for spinal metastases (laminectomy, tumor removal, and mass reduction) significantly reduced pain as well as sensory and motor deficits. We identified male sex, multiple metastases, and pre-existing bowel and bladder dysfunction as predictors of negative outcome.

A curative treatment strategy using tumor debulking surgery combined with immune checkpoint inhibitors for advanced pediatric solid tumors: An in vivo study using a murine model of osteosarcoma.

BACKGROUND/PURPOSE: This study aimed to assess the significance of tumor debulking surgery by using immune checkpoint inhibitors for advanced pediatric solid tumors in a murine model of advanced osteosarcoma. METHODS: In C3H mice, 5 × 106 LM8 (osteosarcoma cell line with a high metastatic potential in the lungs originating from the C3H mouse) cells were transplanted subcutaneously. Thereafter, the mice were divided into 4 groups as follows: the control group received no intervention (CG, n = 5), the surgery group underwent subcutaneous tumor resection (tumor debulking surgery) 11 days after transplantation (SG, n = 10), the immunotherapy group received a cocktail consisting of 200 µg each of three antibodies (anti-Tim-3, anti-PD-L1, and anti-OX-86) intraperitoneally on posttransplantation days 11, 14, 18, and 21 (IG, n = 10), and the combination therapy group, tumor debulking surgery on day 11 and the cocktail intraperitoneally on days 11, 14, 18, and 21 (COMBG, n = 10). Survival curves were plotted by using the Kaplan-Meier method and compared with those plotted using the log-rank test. Next, the lungs of mice in the 4 groups were pathologically evaluated. RESULTS: The COMBG showed significantly longer survival than the other three groups (P ≤ 0.002), whereas the SG and IG revealed no difference in survival rate compared to CG. Pathological evaluations revealed no lung metastasis 16 weeks after tumor transplantation in the survivors of COMBG. CONCLUSIONS: The results of this study suggest that tumor debulking surgery combined with immune checkpoint inhibitors could be a curative treatment for advanced pediatric solid tumors.

Extrauterine inflammatory myofibroblastic tumor: A case report.

•This is the first case report of inflammatory myofibroblastic tumor in the literature to present with extrauterine disease.•A prompt work-up of symptoms may have precluded a tumor debulking procedure.