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Intraperitoneal chemotherapy has shown promising results for the treatment of peritoneal carcinomatosis in gastric cancer. However, the implantation of an intraperitoneal chemotherapy port may be associated with catheter-related complications. The authors describe a case of cutaneous port-site recurrence secondary to tumour seeding from an intraperitoneal chemotherapy access port.

Objective This guideline provides guidance to gynaecologists regarding the use of tissue morcellation in gynaecologic surgery. Outcomes Morcellation may be used in gynaecologic surgery to allow removal of large uterine specimens, thus providing women with a minimally invasive surgical option. Adverse oncologic outcomes of tissue morcellation should be mitigated through improved patient selection, preoperative investigations, and novel techniques that minimize tissue dispersion. Evidence Published literature was retrieved through searches of PubMed and Medline in the spring of 2014 using appropriate controlled vocabulary (leiomyosarcoma, uterine neoplasm, uterine myomectomy, hysterectomy) and key words (leiomyoma, endometrial cancer, uterine sarcoma, leiomyosarcoma, and morcellation). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date limits, but results were limited to English or French language materials. Searches were updated on a regular basis and incorporated in the guideline to July 2017. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Values The quality of evidence in this document was rated using the criteria described in the report of the Canadian Task Force on Preventive Health Care. Benefits, harms, and costs Gynaecologists offer women minimally invasive surgery, and this may involve tissue morcellation and the use of a power morcellator for specimen retrieval. Women should be counselled that in the case of unexpected uterine (sarcoma, endometrial), cervical, and/or tubo-ovarian cancer, the use of a morcellator is associated with increased risk of tumour dissemination. Tissue morcellation should be performed only after complete investigation, appropriate patient selection, and informed consent and by surgeons with appropriate training in the safe practices of tissue morcellation. Summary Statements 1Uterine sarcoma is rare, and as such it is difficult to characterize the absolute risk of occult sarcoma at the time of fibroid surgery. Risk estimates range from 1 in 350 to 1 in 2000. Patient counselling regarding risks should be tailored based on age and other risk factors (II-2). 2Morcellation of any type is contraindicated in women with established cancer, pre-cancerous lesions, or suspected cancer (III). 3When considering morcellation, patients should be counselled about the risks (malignant and non-malignant), benefits, and alternatives as part of the informed consent, especially in women over 50 (III). 4Alternatives to uncontained electromechanical morcellation can be used during fibroid surgery for tissue extraction depending on surgical route, specimen size, surgeon skill/training, and patient preference. If the specimen cannot be removed intact, then no method of tissue extraction can eliminate the risk of iatrogenic tissue dissemination (II-2). 5The benefits of in-bag contained morcellation, including survival rates and ability to prevent dissemination of malignant cells/tissue, have not been established (II-2). 6An unexpected uterine sarcoma treated by primary surgery involving tumour disruption, including morcellation of the tumour, has the potential for intra-abdominal tumour spread and a worse prognosis (II-2). 7Clinicians should be aware of the general complications associated with morcellation beyond the spread of malignant tissue (II-3). Recommendations 1Each patient presenting with uterine leiomyoma should be assessed for the possible presence of malignancy, based on her risk factors and preoperative imaging, although the predictive value of preoperative assessment is limited (III-C). 2If there is a high index of suspicion of a uterine sarcoma prior to surgery, attempts should be made to remove the uterus intact. Myomectomy in perimenopausal and postmenopausal women should be discouraged (III-C). 3Preoperative endometrial biopsy and cervical assessment is recommended in order to avoid morcellation of potentially detectable malignant and pre-malignant conditions of the endometrium and cervix (II-2A). 4Uterine morcellation should be avoided in hereditary cancer syndromes that increase the risk of uterine malignancy (III-C). 5Techniques for morcellation of a uterine specimen vary, and physicians should consider employing techniques that minimize specimen disruption and intra-abdominal spread (III-C). 6Uterine morcellation is contraindicated in women with established or suspected uterine neoplasia (II-2A).

Background: This study evaluated the clinical efficacy of computed tomography (CT)-guided radioactive iodine-125 (125 I) seed implantation in patients with metastatic epidural spinal cord compression (MESCC). Materials and Methods: A cohort of 22 patients with MESCC were retrospectively enrolled. All patients underwent CT-guided 125 I seed implantation therapy via standard procedures. Clinical indexes, including the University of Texas MD Anderson Cancer Center (MDA) criteria for tumor responses, numerical rating scale (NRS) for the degree of pain, Karnofsky Performance Status (KPS) for quality of life, American Spinal Injury Association (ASIA) impairment scale, grade of ESCC, and radiation dose, were evaluated and recorded pre- and post-operation. A follow-up evaluation was performed at least 3 months after the operation. Finally, pre- and post-operative differences in these clinical indexes were compared. Overall survival was recorded. Results: Operations were successfully performed on all patients. A median of 48 (range, 7–103) seeds were implanted in lesions, and the postoperative target verified dose D90 was 11,072.4 ± 1773.5 cGy. Patients were followed for a median of 6 months (range, 3–38 months). The median survival time was 10 months; the response rate was 18/22 (82%); the local control rates at 3, 6, and 12 months were 91.3%, 81.9%, and 81.9%, respectively; and the survival rates were 80%, 50.0%, and 21.9% at 6, 12, and 18 months, respectively. The ESCC grade was significantly lower (P < 0.05). Based on the ASIA impairment scale, the nerve functional reservation, recovery, and decline rates were 63.7% (14/22), 27.3% (6/22), and 9% (2/22), respectively. The NRS and KPS were both significantly improved in the 3rd month of follow-up (P < 0.05). Conclusion: CT-guided 125 I seed implantation represents an effective and safe palliative care for patients with MESCC, which can effectively relieve pain and spinal cord compression and improve nerve function and quality of life.

Summary Many anaesthetists are hesitant to perform epidural blood patch in patients with cancer because of the potential risk of seeding the CNS with malignant cells. Recent evidence suggests that anaesthetists may view malignancy as a relative contraindication to epidural blood patch rather than an absolute contraindication. This review article summarises the clinical dilemma, reviews the existing literature, and proposes a treatment algorithm that includes the utilisation of for the management of post-dural puncture headache in the oncology population.

Cancer progression is characterized by rare, transient events which are nonetheless highly consequential to disease etiology and mortality. Detailed cell phylogenies can recount the history and chronology of these critical events – including metastatic seeding. Here, we applied our Cas9-based lineage tracer to study the subclonal dynamics of metastasis in a lung cancer xenograft mouse model, revealing the underlying rates, routes, and drivers of metastasis. We report deeply resolved phylogenies for tens of thousands of metastatically disseminated cancer cells. We observe surprisingly diverse metastatic phenotypes, ranging from metastasis-incompetent to aggressive populations. These phenotypic distinctions result from pre-existing, heritable, and characteristic differences in gene expression, and we demonstrate that these differentially expressed genes can drive invasiveness. Furthermore, metastases transit via diverse, multidirectional tissue routes and seeding topologies. Our work demonstrates the power of tracing cancer progression at unprecedented resolution and scale.One Sentence SummarySingle-cell lineage tracing and RNA-seq capture diverse metastatic behaviors and drivers in lung cancer xenografts in mice.

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.

We investigated the prognosis of patients with dry pleural dissemination (DPD) of non-small cell lung cancer (NSCLC) and the risk factors of developing to malignant pleural effusion (MPE). We retrospectively reviewed 104 patients with NSCLC and DPD, confirmed surgically from 1996 to 2016. Incidence rate and risk factors of MPE were analyzed statistically. The prognosis of NSCLC patients with MPE was evaluated using the Kaplan–Meier method. The most common histologic type was adenocarcinoma in 95 (91.3%) patients. The median follow-up duration was 65.5 months and the median survival time was 37.7 months. MPE developed in 51 (49%) patients, and the median effusion-free interval was 41.9 months. The median survival time of the patients with and without MPE was not different (41.3 vs 31.7 months, P = .16). No predictive factors for the development of MPE were identified. Fifteen (14.4%) patients underwent invasive procedures for the management of MPE. Almost half of all patients with NSCLC and DPD experienced MPE, and 14.4% patients developed symptomatic MPE requiring invasive procedures. MPE in DPD did not affect the survival in NSCLC patients.

Background Gallbladder cancer is rare, but cancers detected incidentally after cholecystectomy are increasing. The aim of this study was to review the available data for current best practice for optimal management of incidental gallbladder cancer. Methods A systematic PubMed search of the English literature to May 2018 was conducted. Results The search identified 12 systematic reviews and meta-analyses, in addition to several consensus reports, multi-institutional series and national audits. Some 0·25–0·89 per cent of all cholecystectomy specimens had incidental gallbladder cancer on pathological examination. Most patients were staged with pT2 (about half) or pT1 (about one-third) cancers. Patients with cancers confined to the mucosa (T1a or less) had 5-year survival rates of up to 100 per cent after cholecystectomy alone. For cancers invading the muscle layer of the gallbladder wall (T1b or above), reresection is recommended. The type, extent and timing of reresection remain controversial. Observation time may be used for new cross-sectional imaging with CT and MRI. Perforation at initial surgery had a higher risk of disease dissemination. Gallbladder cancers are PET-avid, and PET may detect residual disease and thus prevent unnecessary surgery. Routine laparoscopic staging before reresection is not warranted for all stages. Risk of peritoneal carcinomatosis increases with each T category. The incidence of port-site metastases is about 10 per cent. Routine resection of port sites has no effect on survival. Adjuvant chemotherapy is poorly documented and probably underused. Conclusion Management of incidental gallbladder cancer continues to evolve, with more refined suggestions for subgroups at risk and a selective approach to reresection.

Surgery remains the first choice of cure for early stage lung cancer. However, many patients are diagnosed at advanced stage, and thus miss the opportunity to undergo surgery. As such patients derive limited benefits from chemotherapy or radiotherapy, alternatives focusing on local control have emerged, including iodine‐125 seed implantation. The Interstitial Brachytherapy Society, Committee of Minimally Invasive Therapy in Oncology, Chinese Anti‐Cancer Association organized a group of multidisciplinary experts to develop guidelines for this treatment modality. These guidelines aim to standardize iodine‐125 seed implantation procedures, inclusion criteria, and outcome assessment to prevent and manage procedure‐related complications.

Background Carotid endarterectomy (CEA) is a safe and effective procedure, with a low risk of complications when performed by experienced surgeons. Postoperative infections are particularly rare, reportedly affecting less than 1% of cases. Incisional metastases have not been described. Objective To describe a previously unreported complication, the incisional seeding of metastatic squamous cell carcinoma (SCC) during neck dissection, which presented and was treated as a presumed postoperative neck abscess. Methods Clinical records were reviewed regarding a 73-yr-old female who underwent routine CEA and presented 2 mo postoperatively with neck induration and erythema. Tissue submitted during the initial CEA was reexamined given the updated clinical history. Results Postoperatively, a complex, multi-cystic fluid collection beneath the incision was identified and percutaneously drained. Although cultures were negative, an infection was favored and antibiotic therapy initiated. The patient's symptoms worsened prompting surgical exploration, and tissue sent for pathological examination was consistent with metastatic SCC. Retrospective analysis of a lymph node excised during the initial dissection also revealed tumor deposits, indicating that the surgical site had been seeded during exposure. A primary origin was not identified. Conclusion The time from initial presentation of postoperative complications to a final diagnosis of metastatic SCC was 2 mo, during which time the patient was treated as having a postoperative infection. Further investigations were consistent with diffuse and incurable metastatic disease. This report highlights the diagnostic challenges and potential avoidance strategies when dealing with rare complications following CEA.

Lung metastasis is a primary obstacle in the clinical treatment of metastatic breast cancer. Most patients with lung metastasis eventually die of recurrence. Recurrence may be related to self-seeding, which occurs when circulating tumor cells re-seed into the tumors they originated from (metastasis or carcinoma in situ). Tumor-derived exosomes have been intensively revealed to promote the progression of various cancers. However, whether tumor-derived exosomes play roles in tumor self-seeding has not yet been identified. By establishing a self-seeding nude mouse model, we found that exosomes derived from MDA231-LM2 cells (subpopulations of breast cancer lung metastasis) potentiate the growth of MDA-MB-231 xenografts. More importantly, laser confocal microscopy and flow cytometry results identified that MDA231-LM2-secreted exosomes promote the seeding of MDA231-LM2 cells into MDA-MB-231 xenografts. These findings suggest MDA231-LM2-secreted exosomes as a promising target to treat breast cancer lung metastasis.

Background Development of distant metastases involves a complex multistep biological process termed the invasion-metastasis cascade, which includes dissemination of cancer cells from the primary tumor to secondary organs. NOTCH developmental signaling plays a critical role in promoting epithelial-to-mesenchymal transition, tumor stemness, and metastasis. Although all four NOTCH receptors show oncogenic properties, the unique role of each of these receptors in the sequential stepwise events that typify the invasion-metastasis cascade remains elusive. Methods We have established metastatic xenografts expressing high endogenous levels of NOTCH3 using estrogen receptor alpha-positive (ERα+) MCF-7 breast cancer cells with constitutive active Raf-1/mitogen-associated protein kinase (MAPK) signaling (vMCF-7Raf-1) and MDA-MB-231 triple-negative breast cancer (TNBC) cells. The critical role of NOTCH3 in inducing an invasive phenotype and poor outcome was corroborated in unique TNBC cells resulting from a patient-derived brain metastasis (TNBC-M25) and in publicly available claudin-low breast tumor specimens collected from participants in the Molecular Taxonomy of Breast Cancer International Consortium database. Results In this study, we identified an association between NOTCH3 expression and development of metastases in ERα+ and TNBC models. ERα+ breast tumor xenografts with a constitutive active Raf-1/MAPK signaling developed spontaneous lung metastases through the clonal expansion of cancer cells expressing a NOTCH3 reprogramming network. Abrogation of NOTCH3 expression significantly reduced the self-renewal and invasive capacity of ex vivo breast cancer cells, restoring a luminal CD44low/CD24high/ERαhigh phenotype. Forced expression of the mitotic Aurora kinase A (AURKA), which promotes breast cancer metastases, failed to restore the invasive capacity of NOTCH3-null cells, demonstrating that NOTCH3 expression is required for an invasive phenotype. Likewise, pharmacologic inhibition of NOTCH signaling also impaired TNBC cell seeding and metastatic growth. Significantly, the role of aberrant NOTCH3 expression in promoting tumor self-renewal, invasiveness, and poor outcome was corroborated in unique TNBC cells from a patient-derived brain metastasis and in publicly available claudin-low breast tumor specimens. Conclusions These findings demonstrate the key role of NOTCH3 oncogenic signaling in the genesis of breast cancer metastasis and provide a compelling preclinical rationale for the design of novel therapeutic strategies that will selectively target NOTCH3 to halt metastatic seeding and to improve the clinical outcomes of patients with breast cancer. Electronic supplementary material The online version of this article (10.1186/s13058-018-1020-0) contains supplementary material, which is available to authorized users.

The incidence of ovarian cancer dramatically increases in early menopause but the factors contributing to cancer onset are unclear. Most ovarian cancers originate in the fallopian tube with subsequent implantation of malignant cells into the ovary. However, the events and conditions that lead to cancer cell implantation are unknown. To quantify which conditions are conducive to the seeding of cancer cells in an immunocompetent mouse model, we surgically implanted mouse ovarian cancer cells into the oviducts of syngeneic mice and simulated conditions associated with ovulatory wound repair, incessant ovulation, ovarian surface scarring, and aging. We found that the dominant site of cancer cell seeding was not the ovary but the nearby surgical wound site, which was associated with a strong and persistent inflammatory reaction. Conditions in the ovary associated with inflammation, such as acute ovulatory wound repair, active healing of the scarred ovarian surface, and mouse aging, contributed to increased seeding of the cancer cells to the surgical wound site and tissues surrounding the ovary. Changes in the ovary not accompanied by inflammation, such as completed ovulatory cycles and fully-healed scars on the ovarian surface, did not contribute to increased cancer cell seeding. We conclude that inflammation is the most likely mechanism by which ovulation and postmenopausal events contribute to the increased risk of ovarian cancer.

To determine whether percutaneous transthoracic needle biopsy (PTNB) increased the risk of pleural recurrence in stage I non-small-cell lung cancer (NSCLC). In this retrospective study, we reviewed 830 consecutive patients with stage I NSCLC who underwent curative resection between 2004 and 2010. Cox regression analyses with propensity score matching were performed to identify risk factors for pleural recurrence. Of 830 patients, 540 (65.1%) underwent PTNB before surgery, while 290 (34.9%) underwent preoperative bronchoscopic biopsy or intraoperative wedge resection for a pathological diagnosis. Concomitant pleural recurrence occurred in 42 patients (5.1% [95% CI, 3.8–6.8]; 34 [6.3%] PTNB patients and eight [2.8%] non-PTNB patients) and isolated pleural recurrence took place in 26 patients (3.1% [95% CI, 2.1–4.6]; 20 [3.7%] PTNB patients and 6 [2.1%] non-PTNB patients). On multivariate analysis after matching, only visceral pleural invasion was associated with concomitant pleural recurrence (hazard ratio [HR]=3.367; 95% CI, 1.262–8.986; p=0.015) and isolated pleural recurrence (HR=3.216; 95% CI, 1.037–9.978; p=0.043), while PTNB was associated with neither concomitant nor isolated pleural recurrence (p=0.605 and p=0.963, respectively). Among 540 patients undergoing PTNB, the transfissural approach did not have a significant association with pleural recurrence (p=0.539 and p=0.313, respectively); instead, visceral pleural invasion and microscopic lymphatic invasion were significantly associated with concomitant pleural recurrence, and microscopic lymphatic invasion was associated with isolated pleural recurrence (p

Background: Some surgeons change gloves and instruments after the extirpative phase of cancer surgery with the intent of reducing the risk of local and wound recurrence. Although this practice is conceptually appealing, the evidence that gloves or instruments act as vectors of cancer-cell seeding in the clinical setting is weak. To determine the potential effect of further investigation of this question, we surveyed the practices and beliefs of a broad spectrum of surgeons who operate on cancer patients. Methods: Using a modified Dillman approach, a survey was mailed to all 945 general surgeons listed in the College of Physicians and Surgeons of Ontario public registry. The survey consisted of multiple-choice and free-text response questions. Responses were tabulated and grouped into themes, including specific intraoperative events and surgeon training. Predictive variables were analyzed by chi-square test. Results: Of 459 surveys returned (adjusted response rate: 46%), 351 met the inclusion criteria for retention. Of those respondents, 52% reported that they change gloves during cancer resections with the intent of decreasing the risk of tumour seeding, and 40%, that they change instruments for that purpose. The proportion of respondents indicating that they take measures to protect the wound was 73% for laparoscopic cancer resections and 31% for open resections. Training and years in practice predicted some of the foregoing behaviours. The most commonly cited basis for adopting specific strategies to prevent tumour seeding was “gut feeling,” followed by clinical training. Most respondents believe that it is possible or probable that surgical gloves or instruments harbour malignant cells, but that a cancer recurrence proceeding from that situation is unlikely. Conclusions: There is no consensus on how gloves and instruments should be handled in cancer operations. Further investigation is warranted.

Objectives Malignant ascites is a sign of peritoneal seeding, which is one of the most frequent forms of incurable distant metastasis . Because the development of malignant ascites is associated with an extremely poor prognosis, determining whether it resulted from peritoneal seeding has critical clinical implications in diagnosis, choice of treatment, and active surveillance. At present, the molecular characterizations of malignant ascites are especially limited in case of gastric cancer. We aimed to identify malignant ascites-specific proteins that may contribute to the development of alternative methods for diagnosis and therapeutic monitoring and also increase our understanding of the pathophysiology of peritoneal seeding. Design & methods First, comprehensive proteomic strategies were employed to construct an in-depth proteome of ascitic fluids. Label-free quantitative proteomic analysis was subsequently performed to identify candidates that can differentiate between malignant ascitic fluilds of gastric cancer patients from benign ascitic fluids. Finally, two candidate proteins were verified by ELISA in 84 samples with gastric cancer or liver cirrhosis . Results Comprehensive proteome profiling resulted in the identification of 5347 ascites proteins. Using label-free quantification , we identified 299 proteins that were differentially expressed in ascitic fluids between liver cirrhosis and stage IV gastric cancer patients. In addition, we identified 645 proteins that were significantly expressed in ascitic fluids between liver cirrhosis and gastric cancer patients with peritoneal seeding. Finally, Gastriscin and Periostin that can distinguish malignant ascites from benign ascites were verified by ELISA. Conclusions This study identified and verified protein markers that can distinguish malignant ascites with or without peritoneal seeding from benign ascites. Consequently, our results could be a significant resource for gastric cancer research and biomarker discovery in the diagnosis of malignant ascites.

Introduction Pleural procedures are performed to prove the diagnosis of pleural effusion. This study was to assess the incidence and outcome of pleural procedure-related tumour seeding in lung cancer with malignant pleural effusion, and to review the characteristics of the implanted tumours on computed tomography (CT) images. Methods From January 2008 to December 2010, 165 patients with the diagnosis of lung cancer with malignant pleural effusion, who underwent at least one pleural procedure and had follow-up CT, were included. Two radiologists retrospectively reviewed the presence of implanted tumours and their manifestations on CT images. The incidence of tumour seeding, the time to tumour seeding, and hazard ratios for death associated with the procedures and presence of tumour seeding were evaluated. Multivariable logistic regression analysis was used to identify variables that were independently associated with procedure-related tumour seeding. Results The incidence of procedure-related tumour seeding was 22.4%. Conventional intercostal drainage (ICD) was the independent predictor of tumour seeding. Patients with a history of ICD rapidly developed implanted tumours (P = 0.0319). The estimated mean time of tumour seeding was 2.9 months. There was an increased risk of death with the presence of tumour seeding (HR: 3.35, 95% CI: 1.87-6.01). The majority of CT features showed ill-defined margins with heterogeneous enhancement. Conclusion Pleural procedure-related tumour seeding in lung cancer with malignant pleural effusion is common. There was a significantly increased risk of death with the presence of tumour seeding. The majority of the CT features in implanted tumours were ill-defined margins with heterogeneous enhancement.

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 Intraoperative tumor manipulation may induce the dissemination of occult peritoneal tumor cells (OPTC) into the peritoneal cavity. Methods A systematic review was performed in the PubMed, Embase and Cochrane databases from inception to March 15, 2017. Eligible were studies that analyzed the presence of OPTC in peritoneal fluid, by any method, both before and after resection in adults who underwent intentionally curative pancreatic resection for histopathologically confirmed pancreatic ductal adenocarcinoma in absence of macroscopic peritoneal metastases. Results Four studies with 138 patients met the inclusion criteria. The pooled rate of OPTC prior to tumor manipulation was 8% (95% CI 2%–24%). The pooled detection rate of OPTC in patients in whom OPTC became detectable only after tumor manipulation was 33% (95% CI 15–58%). Only one study (28 patients) reported on survival, which was worse in patients with OPTC (median 11.1 months versus 30.3 months; p = 0.030). Conclusion This systematic review suggests that tumor manipulation induces OPTC in one third of patients with pancreatic cancer. Since data on survival are lacking, future studies should determine the prognostic consequences of tumor manipulation, including the potential therapeutic effect of ‘no-touch’ and minimally invasive resection strategies.

BACKGROUND: Although metastasis is the major cause of mortality in patients with osteosarcoma, little is known about how micrometastases progress to gross metastatic disease. Clinically relevant animal models are necessary to facilitate development of new therapies to target indolent pulmonary metastases. Intratibial injection of human and murine osteosarcoma cell lines have been described as orthotopic models that develop spontaneous pulmonary metastasis over time. However, there is variability in reported injection techniques and metastatic efficiency. QUESTIONS/PURPOSES: We aimed to characterize a widely used murine model of metastatic osteosarcoma, determine whether it is appropriate to study spontaneous pulmonary metastasis by establishing a reliable volume for intratibial injection, determine the incidence of primary tumor and metastatic formation, determine the kinetics of pulmonary metastatic seeding and outgrowth, and the contribution of the primary tumor to subsequent development of metastasis. METHODS: The metastatic mouse osteosarcoma cell line K7M2 was injected into the tibia of mice. The maximum volume that could be injected without leakage was determined using Evan’s blue dye (n = 8 mice). Primary tumor formation and metastatic efficiency were determined by measuring the incidence of primary tumor and metastatic formation 4 weeks after intratibial injection (n = 30). The kinetics of metastatic development were determined by performing serial euthanasia at 1, 2, 3, and 4 weeks after injection (n = 24; five to six mice per group). Number of metastatic foci/histologic lung section and metastatic burden/lung section (average surface area of metastatic lesions divided by the total surface area of the lung) was calculated in a blinded fashion. To test the contribution of the primary tumor to subsequent metastases, amputations were performed 30 minutes, 4 hours, or 24 hours after injection (n = 21; five to six mice per group). Mice were euthanized after 4 weeks and metastatic burden calculated as described previously, comparing mice that had undergone amputation with control, nonamputated mice. Differences between groups were calculated using Kruskal-Wallis and one-way analysis of variance. RESULTS: The maximum volume of cell suspension that could be injected without leakage was 10 μL. Intratibial injection of tumor cells led to intramedullary tumor formation in 93% of mice by 4 weeks and resulted in detectable pulmonary metastases in 100% of these mice as early as 1 week post-injection. Metastatic burden increased over time (0.88% ± 0.58, week 1; 6.6% ± 5.3, week 2; 16.1% ± 12.5, week 3; and 40.3% ± 14.83, week 4) with a mean difference from week 1 to week 4 of -39.38 (p < 0.001; 95% confidence interval [CI], -57.39 to -21.37), showing pulmonary metastatic growth over time. In contrast, the mean number of metastatic foci did not increase from week 1 to week 4 (36.4 ± 33.6 versus 49.3 ± 26.3, p = 0.18). Amputation of the injected limb at 30 minutes, 4 hours, and 24 hours after injection did not affect pulmonary metastatic burden at 4 weeks, with amputation as early as 30 minutes post-injection resulting in a metastatic burden equivalent to tumor-bearing controls (48.9% ± 6.1% versus 40.9% ± 15.3%, mean difference 7.96, p = 0.819; 95% CI, -33.9 to 18.0). CONCLUSIONS: There is immediate seeding of the metastatic site after intratibial injection of the K7M2 osteosarcoma cell line, independent of a primary tumor. This is therefore not a model of spontaneous metastasis. CLINICAL RELEVANCE: This model should not be used to study the early components of the metastatic cascade, but rather used as an experimental model of metastasis. Improved understanding of this commonly used model will allow for proper interpretation of existing data and inform the design of future studies exploring the biology of metastasis in osteosarcoma.

The purpose of this review is to evaluate the current role of percutaneous testicular biopsy in the diagnosis of focal testicular lesions. Percutaneous testicular biopsy can be either fine needle aspiration biopsy or trucut core needle biopsy. It is a well-tolerated and effective procedure useful in small testicular lesions, multifocal lesions, hematological malignancies, and focal lesions in single testis.

To identify differential clinical and imaging findings between intra-abdominal desmoid tumors and peritoneal seeding that developed after surgery for colorectal cancer. 8 patients (9 desmoid tumors) and 11 patients (13 peritoneal seeding masses) were enrolled in our retrospective study. Patients with three or more tumors were excluded. Clinical findings including location of initial tumors, type of surgery, T- and N-stages of initial tumors, time interval between initial surgery and development of intra-abdominal tumors, and level of carcinoembryonic antigen (CEA) were evaluated. Imaging findings of intra-abdominal tumors including size, number, growth rate, location, shape, homogeneity, relative enhancement, and maximum standardized uptake value were evaluated. The Mann–Whitney U test and Fisher’s exact test were used to compare clinical and imaging findings between desmoid tumors and peritoneal seeding. In patients with a desmoid tumor, initial T-stage, initial N-stage, and level of CEA at the time of surgery for intra-abdominal tumor were lower than in patients with peritoneal seeding (p = 0.027, p = 0.033, and p = 0.017). The desmoid tumors were frequently located in the small bowel mesentery (p = 0.018) and were larger at detection (p = 0.041). Round or ovoid shapes on CT images were more frequently observed with the desmoid tumors (p = 0.035). Stage of colorectal cancer, CEA level, and location, size, and shape of new intra-abdominal tumors can be helpful for differentiating between intra-abdominal desmoid tumors and peritoneal seeding in patients with a history of colorectal cancer surgery.

The Canadian Organization of Medical Physicists (COMP), in close partnership with the Canadian Partnership for Quality Radiotherapy (CPQR) has developed a series of Technical Quality Control (TQC) guidelines for radiation treatment equipment. These guidelines outline the performance objectives that equipment should meet in order to ensure an acceptable level of radiation treatment quality. The TQC guidelines have been rigorously reviewed and field tested in a variety of Canadian radiation treatment facilities. The development process enables rapid review and update to keep the guidelines current with changes in technology. This article contains detailed performance objectives and safety criteria for low‐dose‐rate (LDR) permanent seed brachytherapy.

To determine the effect of bile spillage during cholecystectomy on oncological outcomes in incidental gallbladder cancers.Gallbladder cancer (GBC) is rare, but lethal. Achieving complete resection offers the best chance of survival. About 30% of GBCs are discovered incidentally after cholecystectomy for benign pathology. There is an anecdotal association between peritoneal dissemination and bile spillage during the index cholecystectomy. However, no population-based studies are available that measure the consequences of bile spillage on patient outcomes.We conducted a retrospective cohort comparison of patients with incidental GBC. All cholecystectomies and cases of GBC in Alberta, Canada, from 2001 to 2015, were identified. GBCs discovered incidentally were included. Operative events leading to bile spillage were reviewed. Patient outcomes were compared between cases of bile spillage versus no contamination.In all, 115,484 cholecystectomies were performed, and a detailed analysis was possible in 82 incidental GBC cases. In 55 cases (67%), there was bile spillage during the index cholecystectomy. Peritoneal carcinomatosis occurred more frequently in those with bile spillage (24% vs 4%; P = 0.0287). Patients with bile spillage were less likely to undergo a radical re-resection (25% vs 56%; P = 0.0131) and were less likely to achieve an R0 resection margin [odds ratio 0.19, 95% confidence interval (CI) 0.06-0.55]. On Cox regression modeling, bile spillage was an independent predictor of shorter disease-free survival (hazard ratio 1.99, 95% CI 1.07-3.67).For incidentally discovered GBC, bile spillage at the time of index cholecystectomy has measureable adverse consequences on patient outcomes. Early involvement of a hepatobiliary specialist is recommended where concerning features for GBC exist.

Dissemination of the tumor within surgical field increases the risk of local recurrences. Fungating soft tissue tumors present a special risk of contamination in the attempt to perform wide resections. We hypothesized that adequate tumor coverage at resection could prevent tumor spilling and superficial dissemination in the operation field. For this purpose we used swabs to soak secretions. Incise drapes were put over swabs to seal the tumor. Double row skin staples were placed at the edge of the adhesive drapes for lift-off-prevention. We present eight patients treated with wide resection (3 myxofibrosarcomas, 2 malignant melanomas, 1 spindle cell sarcoma, 1 basal cell carcinoma, and 1 exulcerated lipoma). No complications were observed using this technique. An intraoperative local control, confirmed histologically, was achieved in all patients. Tumor covering could help local tumor control at fungating tumor resection.

Background and Aims During endoscopic full-thickness resection (EFTR) for cancers, whether exposure of the lumen to the abdominal cavity during the procedure is acceptable is controversial because of the potential risk of tumor cell seeding. To assess the possibility of transplantation as a result of contact with tumor cells during the procedure, we prospectively investigated the ability of cancer cells to be detached by touching the tumor surface. Methods In 48 patients with a single early gastric cancer resected by endoscopic submucosal dissection, stamp cytology was performed by touching the surface of the specimens to glass slides. Samples were obtained from cancerous and noncancerous areas, constituting the study and control groups, respectively. The detection rate of malignant class IV or V (C-IV/C-V) samples was investigated with Papanicolaou staining. The rate of CD44v9-positive cases, a cancer stem cell marker, was assessed in C-IV/C-V samples with immunohistochemical staining. Results Detection rates of C-IV/C-V samples in the cancerous group (53/192 slides, 27.6%) differed significantly from those of the C-IV/C-V samples in the noncancerous group (0/96 slides, 0%). Among the 53 slides of C-IV/C-V samples in the cancerous group, CD44v9 cells were expressed in 18 slides (34.0%). Conclusions These data suggest that cancer cells, including cancer stem cells, in early gastric cancers are easily detached via contact with the tumor surface. In EFTR, a nonexposure approach is recommended to avoid the risk of iatrogenic cancer cell seeding via contact with and transplantation of cancer cells.

Percutaneous endoscopic gastrostomy (PEG) has become a mainstay in providing enteral access for patients with obstructive head, neck and esophageal tumors. Tumor cell implantation is a rare complication in patients with aerodigestive cancers, who have undergone PEG tube placement. The objective of this review is to determine the incidence and contributing risk factors leading to the implantation of metastases into the abdominal wall following PEG placement. A comprehensive review of the literature in PUBMED (2008-2018) was performed. The literature search revealed reports of more than 50 cases of abdominal wall metastases after PEG placement. As most of these studies were case reports, the exact rate of metastasis remains unknown. Generally pharyngoesophageal location of primary cancer (100%), squamous cell histology (98%), poorly differentiated tumor cells (92%), advanced pathological stage (97%), and large primary cancer size were identified as strong risk factors for the development of stomal metastasis. Abdominal wall metastases following PEG placement are a rare but serious complication in patients with head and neck malignancy. (www.actabiomedica.it)

Purpose Vitreous seeding remains the primary reason for treatment failure in eyes with retinoblastoma (Rb). Systemic and intra-arterial chemotherapy, each with its own inherent set of complications, have improved salvage rates for eyes with advanced disease, but the location and biology of vitreous seeds present a fundamental challenge in developing treatments with minimal toxicity and risk. The aim of this study was to target the platelet-derived growth factor (PDGF)- PDGF-receptor β (PDGFRβ) signaling pathway and investigate its role in the growth of Rb seeds, apoptotic activity, and invasive potential. Methods We performed ex vivo analyses on vitreous samples from Rb patients that underwent enucleation and from patient-derived xenografts. These samples were evaluated by quantitative PCR, immunohistochemistry, and ELISA. The effects of disruption of the PDGF-PDGFRβ signaling pathway, both by pharmacologic and genomic knockdown approaches, were evaluated in vitro by cell proliferation and apoptotic assays, quantitative PCR analyses, Western blotting, flow cytometry, and imaging flow cytometry. A three-dimensional cell culture system was generated for in-depth study of Rb seeds. Results Our results demonstrated that PDGFRβ signaling is active in the vitreous of Rb patients and patient-derived xenografts, sustaining growth and survival in an AKT-, MDM2-, and NF-κB-dependent manner. The novel three-dimensional cell culture system mimics Rb seeds, as the in vitro generated spheroids have similar morphologic features to Rb seeds and mimicked their natural physiology. Conclusions Targeting the PDGFRβ pathway in vitro reduces Rb cell growth, survival, and invasiveness and could augment current therapies. This represents a novel signaling pathway for potential targeted therapy to further improve ocular survival in advanced Rb.

Purpose Current melphalan-based regimens for intravitreal chemotherapy for retinoblastoma vitreous seeds are effective but toxic to the retina. Thus, alternative agents are needed. Based on the known biology of histone deacetylases (HDACs) in the retinoblastoma pathway, we systematically studied whether the HDAC inhibitor belinostat is a viable, molecularly targeted alternative agent for intravitreal delivery that might provide comparable efficacy, without toxicity. Methods In vivo pharmacokinetic experiments in rabbits and in vitro cytotoxicity experiments were performed to determine the 90% inhibitory concentration (IC90). Functional toxicity by electroretinography and structural toxicity by optical coherence tomography (OCT), OCT angiography, and histopathology were evaluated in rabbits following three injections of belinostat 350 µg (2× IC90) or 700 µg (4× IC90), compared with melphalan 12.5 µg (rabbit equivalent of the human dose). The relative efficacy of intravitreal belinostat versus melphalan to treat WERI-Rb1 human cell xenografts in rabbit eyes was directly quantified. RNA sequencing was used to assess belinostat-induced changes in RB cell gene expression. Results The maximum nontoxic dose of belinostat was 350 µg, which caused no reductions in electroretinography parameters, retinal microvascular loss on OCT angiography, or retinal degeneration. Melphalan caused severe retinal structural and functional toxicity. Belinostat 350 µg (equivalent to 700 µg in the larger human eye) was equally effective at eradicating vitreous seeds in the rabbit xenograft model compared with melphalan (95.5% reduction for belinostat, P < 0.001; 89.4% reduction for melphalan, P < 0.001; belinostat vs. melphalan, P = 0.10). Even 700 µg belinostat (equivalent to 1400 µg in humans) caused only minimal toxicity. Widespread changes in gene expression resulted. Conclusions Molecularly targeted inhibition of HDACs with intravitreal belinostat was equally effective as standard-of-care melphalan but without retinal toxicity. Belinostat may therefore be an attractive agent to pursue clinically for intravitreal treatment of retinoblastoma.

Aim To evaluate the analgesic efficacy, safety, and local tumor control of iodine-125 (125I) seed brachytherapy (BT) for the management of spine and bone metastases. Methods A systematic literature search was conducted using PubMed, the Cochrane Library, and Scopus databases. Data regarding patient demographics, tumor characteristics, procedural parameters, and clinical outcomes were extracted and analyzed. Results Fourteen studies (7 prospective, 7 retrospective) were included, accounting for 689 patients, in our review. Analgesic efficacy was assessed at baseline and various postoperative time points. Significant improvement in pain was noted at 4- and 24-week follow-ups (p Conclusion 125I seed BT, alone or in conjunction with cement augmentation, may be a viable salvage therapy in appropriately selected patients. However, further studies are needed to analyze the long-term efficacy of this intervention as a palliative and curative modality.

Case Presentation A 51-year-old woman was found to have a new 14 × 6 mm soft tissue mass under the right serratus muscle on a CT scan of the chest performed for routine surveillance due to her history of stage I lung cancer. A follow-up CT scan performed 4 months later showed that the mass had increased in size to 22 × 8 mm. The patient presents to the oncology clinic to discuss the results of the CT scan. She has no pain or swelling on the right lateral chest and no cough, fever, or shortness of breath. She is at her baseline health with good appetite and functional status.

Patients with bladder cancer who present with hydronephrosis may require drainage of the affected kidney before receiving further cancer treatment. Drainage can be done by retrograde stenting or percutaneously. However, retrograde stenting carries the risk of tumor cell spillage to the upper urinary tract. The aim of this study was to evaluate whether patients with bladder cancer are at higher risk for upper urinary tract recurrence if retrograde stenting has been performed prior to radical cystectomy.We retrospectively analyzed the records of 1,005 consecutive patients with bladder cancer who underwent radical cystectomy at our department between January 2000 and June 2016. Negative intraoperative ureteral margins were mandatory for study inclusion. Patients received regular followup according to our institutional protocol, including imaging of the upper urinary tract and urine cytology.Preoperative drainage of the upper urinary tract was performed in 114 of the 1,005 patients (11%), including in 53 (46%) by Double-J® stenting and in 61 (54%) by percutaneous nephrostomy. Recurrence developed in the upper urinary tract in 31 patients (3%) at a median of 17 months after cystectomy, including 7 of 53 (13%) in the Double-J group, 0% in the nephrostomy group and 24 of 891 (3%) in the no drainage group. Multivariate regression analysis revealed a higher risk of upper urinary tract recurrence if patients underwent Double-J stenting (HR 4.54, 95% CI 1.43-14.38, p = 0.01) and preoperative intravesical instillations (HR 2.94, 95% CI 1.40-6.16, p = 0.004).Patients who undergo Double-J stenting prior to radical cystectomy are at higher risk for upper urinary tract recurrence. If preoperative upper urinary tract drainage is required, percutaneous drainage might be recommended.