Tumor Seeding Post Nutritional Support Implementation: A Rare Complication; A Scoping Review.

Patients with cancer are at risk of malnutrition because of reduced food intake, thus making oral intake challenging. Thus, nutritional support is used to provide the nutrient requirements. Feeding tube site implantation among patients with cancer has been reported after endoscopic feeding gastrostomy installation. This manuscript aims to further explore this phenomenon using a structured database review. Among 33 seeding cases included in this review, case reports (70 %) were the most common study design, predominantly using percutaneous endoscopic gastrostomy via the pull method. The duration between tube implantation and seeding detection ranged from 7.12 ± 3.7 months, with some missing data among the included studies. The most common primary cancer diagnosis was head and neck cancer. Tumor seeding was higher among male patients than that in female patients. However, large-scale, statistically powered studies are needed to further investigate this complication.

Efficacy of intravitreal injections of melphalan in the treatment of retinoblastoma vitreous seeding.

BACKGROUND: The introduction of intravitreal injections of melphalan (IVIM) has significantly improved the efficacy of retinoblastoma treatment and the prognosis for eye preservation. OBJECTIVES: To evaluate the results of using IVIM to treat retinoblastoma vitreous seeding. MATERIAL AND METHODS: This was a clinical, retrospective, single-center study. Twenty-six children (27 eyes) who met all of the following inclusion criteria qualified for the study: 1) active vitreous seeding at the time of retinoblastoma diagnosis; 2) IVIM performed between 1 January 2017 and 30 September 2020; and 3) a minimum follow-up period of 12 months since the last IVIM. Doses of 20-40 µg melphalan per injection were used. RESULTS: The eye observation period from the last IVIM to the last ophthalmic examination averaged 32.41 months (median 30.00; range 13.00-56.00). Success (no active tumors in the vitreous body) was achieved in 24 eyes (88.9%), and a doubtful result (recurrence in the retina with a difficult-to-determine etiology) in 2 eyes (7.4%). In 1 eye (3.7%), despite treatment, active tumors were still present in the vitreous body. Out of all 27 eyes, 4 eyeballs were removed, but the direct cause of enucleation was not vitreous seeding. There were no complications in the form of intraocular inflammation, extraocular retinoblastoma or distant metastases. There was 1 case of anterior uveitis and 1 case of cataract. CONCLUSIONS: The IVIM is a highly effective and safe form of treatment for retinoblastoma vitreous seeding.

Toxicity to intravitreal melphalan in a patient with retinoblastoma.

Objective: Description of melphalan's toxicity in retinoblastoma treatment. Methods: Clinical case report. Results: We presented a case of unilateral retinoblastoma with vitreous seeding at diagnosis, in which the use of intravitreal melphalan produced many adverse reactions. Conclusions: Vitreous seedings have been one of the most important challenges in retinoblastoma treatment. Intravitreal melphalan has achieved the regression of vitreous seedings in a large percentage of cases. It is a safe treatment; however, it can produce toxicity, even with the standard dose of 20-30 µg, which has been poorly documented. Exhaustive follow-up of patients is recommended for an early diagnosis of possible adverse effects. Abbreviations: OS = left eye, RI = magnetic resonance imaging, OCT = optical coherence tomography.

Tumor seeding following CT- guided transthoracic needle biopsy in lung cancer. A case report.

As a result of advances in the treatment of lung cancer, the life expectancy of lung cancer patients has improved significantly, but it remains the leading cause of cancer death worldwide. For decades, most of the initial tumor biopsies have been obtained by bronchoscopy or computed tomography (CT)-guided transthoracic lung biopsy without concerning reports of cancer seeding following the latter. In this case report we discuss the patient history of a 56-year old women with low-differentiated squamous cell lung cancer who developed tumor seeding following a CT-guided transthoracic biopsy 11 months after the intervention. This is put into context reviewing former and current literature.

In vivo deuterium magnetic resonance imaging of xenografted tumors following systemic administration of deuterated water.

In vivo deuterated water (2H2O) labeling leads to deuterium (2H) incorporation into biomolecules of proliferating cells and provides the basis for its use in cell kinetics research. We hypothesized that rapidly proliferating cancer cells would become preferentially labeled with 2H and, therefore, could be visualized by deuterium magnetic resonance imaging (dMRI) following a brief period of in vivo systemic 2H2O administration. We initiated systemic 2H2O administration in two xenograft mouse models harboring either human colorectal, HT-29, or pancreatic, MiaPaCa-2, tumors and 2H2O level of ~ 8% in total body water (TBW). Three schemas of 2H2O administration were tested: (1) starting at tumor seeding and continuing for 7 days of in vivo growth with imaging on day 7, (2) starting at tumor seeding and continuing for 14 days of in vivo growth with imaging on day 14, and (3) initiation of labeling following a week of in vivo tumor growth and continuing until imaging was performed on day 14. Deuterium chemical shift imaging of the tumor bearing limb and contralateral control was performed on either day 7 of 14 after tumor seeding, as described. After 14 days of in vivo tumor growth and 7 days of systemic labeling with 2H2O, a clear deuterium contrast was demonstrated between the xenografts and normal tissue. Labeling in the second week after tumor implantation afforded the highest contrast between neoplastic and healthy tissue in both models. Systemic labeling with 2H2O can be used to create imaging contrast between tumor and healthy issue, providing a non-radioactive method for in vivo cancer imaging.

Portsite metastasis of adenocarcinoma after laparoscopic cholecystectomy with an unknown primary tumor: a case report.

Port site metastasis of adenocarcinoma after laparoscopic cholecystectomy with an unknown primary tumor is rare. To the best of our knowledge, there are only four such cases reported worldwide. We report a woman in her 70s with cholecystitis who underwent laparoscopic cholecystectomy. Intraoperative laparoscopic exploration did not reveal an abdominal tumor, and postoperative gallbladder pathology did not suggest malignancy. However, 11 months later, she developed an incisional mass in the epigastric port site. In another 6 months, magnetic resonance imaging revealed an abdominal wall tumor. Therefore, she underwent radical resection of the subcutaneous tumor, and postoperative pathology revealed adenocarcinoma. However, no primary tumor was found after systemic imaging examination.

Needle tract seeding and malignant transformation of hepatocellular adenoma into well-differentiated hepatocellular carcinoma in a dog.

An 11-year-old neutered female Golden Retriever was referred for investigation of marked increases in liver enzyme activities. Abdominal ultrasound revealed a large pedunculated liver mass. Diagnosis of hepatocellular adenoma (HCA) was made when the mass was excised after a first unsuccessful attempt through ultrasound-guided core-needle biopsy. One and a half years after presentation, a nodule embedded between muscles of the abdominal wall appeared. The mass was first diagnosed as a well-differentiated hepatocellular carcinoma (HCC) through cytologic examination, which was later confirmed with histopathology. Ki 67 immunostaining of the abdominal wall nodule showed an increased immunoreactivity compared with the liver mass. Therefore, the present case documents the first needle-tract seeding of a hepatocellular epithelial tumor with possible malignant transformation of HCA into a well-differentiated HCC in a dog.

Gastric intramural metastasis caused by needle tract seeding after preoperative fine needle aspiration for pancreatic body cancer subsequently resected by total pancreatectomy: a case report and literature review.

BACKGROUND: Recently, there has been an increase in the number of reports of needle tract seeding (NTS) of tumor cells after a biopsy as one of the adverse events related to endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA). In most of the previously reported cases of NTS in pancreatic cancer, distal pancreatectomy was performed as the initial surgery, following which metachronous metastasis was discovered in the gastric wall, whose localization matched the puncture route of the EUS-FNA. We report a case of early metastasis from pancreatic cancer in the gastric wall, which was postulated to be caused by NTS. Our patient underwent a total pancreatectomy (TP), and the NTS was resected synchronously. CASE PRESENTATION: A 70-year-old woman with a diagnosis of pancreatic head-body-tail cancer presented to our department for surgery. Transgastric EUS-FNA and biopsy established the histological diagnosis in her case. We administered neoadjuvant chemotherapy (NAC) to the patient and performed a TP. Histopathological and immunohistochemical examination subsequently confirmed the diagnosis of pT3N1aM1 pancreatic adenocarcinoma and its gastric metastasis, which was caused by NTS. It is postulated that the tumor cells of NTS had progressed to develop the metastatic lesion in the gastric wall during the NAC period. This was also resected during the initial surgery. The patient developed an early postoperative recurrence in the peritoneum 8 months after the surgery. CONCLUSION: In pancreatic head cancer cases, the puncture route is often included in the resection area of radical surgery, and NTS is seldom considered as a potential clinical problem. However, NTS can progress rapidly and may be associated with early recurrence of malignancy. Therefore, when transgastrointestinal puncture is performed for the diagnosis of pancreatic cancer, the treatment strategy should be established considering the potential development of NTS.

Retinoblastoma seeds: impact on American Joint Committee on Cancer clinical staging.

AIM: To investigate whether the American Joint Committee on Cancer (AJCC) clinical category cT2b needs to be subclassified by the type and distribution of retinoblastoma (RB) seeding. METHODS: Multicentre, international registry-based data were collected from RB centres enrolled between January 2001 and December 2013. 1054 RB eyes with vitreous or subretinal seeds from 18 ophthalmic oncology centres, in 13 countries within six continents were analysed. Local treatment failure was defined as the use of secondary enucleation or external beam radiation therapy (EBRT) and was estimated with the Kaplan-Meier method. RESULTS: Clinical category cT2b included 1054 eyes. Median age at presentation was 16.0 months. Of these, 428 (40.6%) eyes were salvaged, and 430 (40.8%) were treated with primary and 196 (18.6%) with secondary enucleation. Of the 592 eyes that had complete data for globe salvage analysis, the distribution of seeds was focal in 143 (24.2%) and diffuse in 449 (75.8%). The 5-year Kaplan-Meier cumulative globe-salvage (without EBRT) was 78% and 49% for eyes with focal and diffuse RB seeding, respectively. Cox proportional hazards regression analysis confirmed a higher local treatment failure risk with diffuse seeds as compared with focal seeds (hazard rate: 2.8; p<0.001). There was insufficient evidence to prove or disprove an association between vitreous seed type and local treatment failure risk(p=0.06). CONCLUSION: This international, multicentre, registry-based analysis of RB eyes affirmed that eyes with diffuse intraocular distribution of RB seeds at diagnosis had a higher risk of local treatment failure when compared with focal seeds. Subclassification of AJCC RB category cT2b into focal vs diffuse seeds will improve prognostication for eye salvage.

Addition of intravitreal carboplatin with melphalan for management of vitreous seeding in retinoblastoma.

PURPOSE: To evaluate the efficacy and toxicity of intravitreal carboplatin plus melphalan for the treatment of vitreous seeds in eyes with retinoblastoma (RB). METHODS: This retrospective series at a tertiary referral center included 22 consecutive RB patients who had received intravitreal carboplatin (16 µg per 0.05 ml) combined with melphalan (30 µg in 0.03 ml) [IVi (Ca-Me)] for treatment of vitreous seeds. Tumor control and drug toxicities were recorded. RESULTS: There were 22 eyes of 22 patients, divided into primary group (n = 13) without history of previous intravitreal chemotherapy (IViC) and refractory group (n = 9) with history of previous IViC using melphalan and/or topotecan. The demographics and clinical findings of the primary and refractory groups did not differ significantly. The 6-month follow-up revealed complete vitreous seed control (77% vs. 89%, p = 0.47). Vitreous seed recurrence was detected in 1 eye of each group at 6 months. During the next 18-month follow-up period, no recurrence of seed was observed. The response to IVi (Ca-Me) was not significantly influenced by previous IViC (p = 0.70), primary systemic or intra-arterial chemotherapy (p = 0.45), or the type of regression (p = 0.35). The most common tumor treatment complications were retinal detachment (RD) (n = 2), early hypotony (n = 2) and late hypotony (n = 4, unrelated), cataract (n = 2), and severe pigment dispersion (n = 1). Enucleation was performed in 8 eyes, for total RD (n = 1), phthisis bulbi (n = 5), and extensive solid tumor recurrence (n = 2). There was no case of orbital invasion, systemic metastasis, or death. CONCLUSION: Based on this interventional case series for primary and refractory vitreous RB seeds, carboplatin plus melphalan therapy may be effective with few toxic side effects.

A typical anterior retinoblastoma: diagnosis by aqueous humor cell-free DNA analysis.

BACKGROUND: Aqueous humor from eyes with active retinoblastoma contains tumor-derived cell-free DNA. MATERIALS AND METHODS: Single retrospective case report. RESULTS: A 13-year-old girl with acute right eye pain and redness was diagnosed with hypertensive anterior uveitis. Following initial management, she was referred to ocular oncology for an atypical clinical picture. Multiple seeds were noted 360 degrees in the anterior chamber, at the equator of the lens and canal of Petit, and ultrasound biomicroscopy identified a temporal pars plana lesion. While aqueous humor cytology was inconclusive for malignancy, targeted next-generation sequencing of aqueous cell-free DNA identified biallelic RB1 full gene deletion, confirming the diagnosis of retinoblastoma. Partial regression followed three cycles of systemic carboplatin, etoposide, and vincristine and three intracameral melphalan injections. Four months later, she had recurrence of the primary tumor and increase in seeding and received the investigational sustained release episcleral topotecan chemoplaque. Stable regression was achieved to 28-month follow-up, with no detectable aqueous cell-free DNA. CONCLUSIONS: RB1 sequencing analysis of tumor-derived cell-free DNA from aqueous humor can confirm the diagnosis of retinoblastoma in cases of diagnostic uncertainty.

Safety of percutaneous, image-guided biopsy of hepatocellular carcinoma with and without concurrent ablation.

PURPOSE: To determine the prevalence of adverse events after image-guided biopsy of histologically proven hepatocellular carcinomas (HCC) using a standardized, indirect access, coaxial biopsy technique. METHODS: In this IRB-approved, HIPAA compliant, and retrospective study, we evaluated all consecutive adult patients from 2011 to 2016 who underwent image-guided biopsy of HCC with and without concurrent ablation. Tumor seeding was defined as any new lesion along the needle tract on subsequent imaging. Adverse events were graded using both the Clavien-Dindo Complication Classification system and the most recently proposed Society of Interventional Radiology (SIR) Adverse Event Classification System. RESULTS: A total of 383 patients underwent 398 biopsies (64 ± 11 years; 112 women, 271 men). Most patients (282; 71%) underwent concurrent ablation. Adverse events occurred after 18 biopsies (4.5%): 13 were Grade I (Clavien-Dindo) or minor (SIR) and included hematoma (7), hepatic vein thrombus (2), portal vein thrombus (2), moderate pleural effusion (1), and small pneumothorax (1). The remaining 5 (1.3%) adverse events were classified as Grade II-IIIa (Clavien-Dindo) or moderate (SIR) and included hematoma requiring blood products (n = 1), arrhythmia (n = 1), and symptomatic pleural effusions requiring treatment (n = 3). Baseline age, sex, cause of liver disease, HCC diameter, and HCC grade were not associated with adverse events. There were no tumor seeding events after a median follow-up of 611 days (interquartile range of 211-1104). CONCLUSION: Percutaneous image-guided tissue sampling using a standardized, indirect access, coaxial technique can be performed safely with and without concurrent ablation by trained cross-sectional interventional radiologists at a tertiary liver transplant center.

Aqueous Seeding in Retinoblastoma: Classification and Clinicopathologic Correlation.

PURPOSE: To correlate the clinical types of aqueous seeds with histopathologic characteristics in primarily enucleated eyes with retinoblastoma (RB). DESIGN: Retrospective study. PARTICIPANTS: Twenty-five patients with RB. METHODS: Clinicopathologic correlation of aqueous seeds in 25 eyes that underwent primary enucleation and showed evidence of aqueous seeds. MAIN OUTCOME MEASURES: Histopathologic characteristics of aqueous seeds. RESULTS: All 25 enucleated eyes were classified as group E RB based on the International Classification of Intraocular Retinoblastoma. Clinically, type 1 aqueous seeds were noted in 9 (36%) eyes, type 2 in 8 (32%), and type 3 in 8 (32%). Based on histopathology, type 1 seeds were defined as individual tumor cells admixed with macrophages and nonviable tumor cells. Type 2 seeds were defined as spheres and classified into 2 subtypes: (1) spheres without central necrosis containing solid clusters of tumor cells and (2) spheres with central necrosis containing a central core of necrotic cells surrounded by viable tumor cells. Type 3 seeds were defined as tumor cells admixed with macrophages and red blood cells sedimented at an angle. Aqueous seeding involved both anterior (n = 25; 100%) and posterior (n = 18; 72%) chambers. Significant infiltration of RB into the intraocular tissue (Schlemm canal, trabecular meshwork, ciliary body, choroid, optic nerve, and sclera) was noted in 23 cases (92%). Compared with eyes with type 1 and 2 seeds, eyes with type 3 seeds were more commonly associated with ciliary body infiltration (41% vs. 88%, respectively; P = 0.04). Over a mean follow-up period of 57 months (median, 49 months; range, <1-175 months), metastasis and death were noted in 3 patients (12%). CONCLUSIONS: Similar to vitreous seeds in RB, aqueous seeds have 3 distinct histopathologic types. Posterior chamber seeds were noted in 72% of cases presenting with anterior chamber (AC) seeds, indicating the need for the treatment of both the chambers whenever conservative treatment is attempted in suitable cases. Most (92%) cases with primary aqueous seeding are associated with other high-risk histopathology features, suggesting a cautious approach to conservative management in these cases.

Inhibition of ADAM17 impairs endothelial cell necroptosis and blocks metastasis.

Metastasis is the major cause of death in cancer patients. Circulating tumor cells need to migrate through the endothelial layer of blood vessels to escape the hostile circulation and establish metastases at distant organ sites. Here, we identified the membrane-bound metalloprotease ADAM17 on endothelial cells as a key driver of metastasis. We show that TNFR1-dependent tumor cell-induced endothelial cell death, tumor cell extravasation, and subsequent metastatic seeding is dependent on the activity of endothelial ADAM17. Moreover, we reveal that ADAM17-mediated TNFR1 ectodomain shedding and subsequent processing by the γ-secretase complex is required for the induction of TNF-induced necroptosis. Consequently, genetic ablation of ADAM17 in endothelial cells as well as short-term pharmacological inhibition of ADAM17 prevents long-term metastases formation in the lung. Thus, our data identified ADAM17 as a novel essential regulator of necroptosis and as a new promising target for antimetastatic and advanced-stage cancer therapies.

Oncological Resection for Liver Malignancies: Can the Laparoscopic Approach Provide Benefits?

Laparoscopic surgery has become an increasingly popular alternative approach to open surgery, resulting in a paradigm shift in liver surgery. Although laparoscopic liver resection (LLR) was initially indicated for small benign and peripheral tumors, at present more than half of LLRs are performed in malignant tumors. Several studies have reported the feasibility of LLR in malignant disease and suggested various short-term benefits compared to open liver resection, including decreased blood loss and postoperative complications and a shorter hospital stay. Although these benefits are important to surgeons, patients, and providers, the main goal of surgery for malignancies is to achieve a maximum oncologic benefit. The relevance of the laparoscopic approach must be assessed in relation to the possibility of respecting basic oncological rules and the expertise of the center. Easy LLRs can be safely performed by most surgeons with minimum expertise in liver surgery and laparoscopy, and can therefore probably provide an oncological benefit. On the other hand, intermediate or difficult LLRs require technical expertise and an oncological benefit can only be achieved in expert centers. Technical standardization is the only way to obtain an oncological benefit with this type of resection, and many problems must still be solved.

Possible tumour cell reimplantation during curative endoscopic therapy of superficial Barrett's carcinoma.

BACKGROUND AND AIMS: Endoscopic resection has been established as curative therapy for superficial cancer arising from Barrett's oesophagus (BE); recurrences are very rare. Based on a case series with unusual and massive early recurrences, we analyse the issue of tumour cell reimplantation. METHODS: This hypothesis was developed on the basis of two out of seven patients treated by circumferential (n=6) or nearly circumferential (n=1) en bloc and R0 endoscopic resection of T1 neoplastic BE. Subsequently, a prospective histocytological analysis of endoscope channels and accessories was performed in 2 phases (cytohistological analysis; test for cell viability) in 22 different oesophageal carcinoma patients undergoing endoscopy. Finally, cultures from two oesophageal adenocarcinoma cell lines were incubated with different triamcinolone concentrations (0.625-10 mg/mL); cell growth was determined on a Multiwell plate reader. RESULTS: Cancer regrowth in the two suspicious cases (male, 78/71 years) occurred 7 and 1 months, respectively, after curative tumour resection. Subsequent surgery showed advanced tumours (T2) with lymph node metastases; one patient died. On cytohistological examinations of channels and accessories, suspicious/neoplastic cells were found in 4/10 superficial and in all 5 advanced cancers. Further analyses in seven further advanced adenocarcinoma cases showed viable cells in two channel washing specimens. Finally, cell culture experiments demonstrated enhanced tumour cell growth by triamcinolone after 24 hours compared with controls. CONCLUSIONS: Tumour cell reimplanation from contaminated endoscopes and accessories is a possible cause of local recurrence after curative endoscopic therapy for superficial Barrett carcinoma; also, corticosteroid injection could have promoted tumour regrowth in these cases.