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BACKGROUND/AIM Computed tomography and positron emission tomography cannot detect all minute distant metastases and fully evaluate extensive vascular invasion in patients with pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to investigate predictors of laparotomy only and palliative surgery in PDAC patients planning surgical resection. PATIENTS AND METHODS We reviewed 239 PDAC patients planning surgical resection. Patients were divided into two groups based on resection status. Multivariate analyses were performed to identify predictors of unresectable disease at laparotomy. RESULTS Twenty-five patients had unresectable disease at laparotomy. Multivariate analysis revealed that anatomical borderline resectable status (yes/no) (HR=5.458, p=0.012), pretreatment CA19-9 (>260/≤260 ng/ml) (HR=4.907, p=0.041), and tumor size (>25/≤25 mm) (HR=21.42, p=0.004) were associated with unresectable disease at laparotomy. CONCLUSION Borderline resectable status, pretreatment CA19-9, and tumor size were closely associated with unresectable disease at laparotomy in PDAC patients planning surgical resection.

Introduction: Malignant pleural mesothelioma (MPM) has limited treatment options with minimal new therapy approvals for unresectable disease in the past 15 years. However, considerable work has occ...

CA19-9 serum has been suggested as a marker of unresectability but different cut-off levels have been published. A cut-off of 500 U/ml is currently considered in an international consensus as biological criteria of borderline resectable pancreatic adenocarcinoma. To evaluate whether serum CA19-9 threshold of 500 U/ml could be adequate predictor of resectability in pancreatic adenocarcinoma. Multicenter, observational, prospective study performed in Spain including 203 patients diagnosed with pancreatic adenocarcinoma. 43 (21.2%) cases were resectable and 160 (78.8%) unresectable. Among the 176 preoperative CA19-9 available values, 98 (58.3%) were ≤ 500 U/ml and 73 (42.7%) > 500 U/ml. Resectability rate in those patients with CA19-9 ≤ 500 U/ml was 60% while it was found to be 18% when CA19-9 > 500 U/ml. Statistical model to predict resectability based on CA19-9 provide an AUC of 0.6618 (95% CI 0.53–0.83) when only CA19-9 values > 500 U/ml are studied. Serum levels of CA19-9 higher than 500 U/ml are indicative of unresectable disease, however reduced sensitivity and specificity lead to a limited clinical applicability for resectability.

There is a lack of clear guidelines on optimal radiotherapy dose regimen for elderly breast cancer patients. This review summarizes the current evidence on role of hypofractionated radiotherapy in elderly breast cancer. Also, suggestions have been provided on the best fractionation approaches based on current evidence. Hypofractionated radiotherapy is feasible and well tolerated in elderly breast cancer patients with both early and locally advanced disease. Ultra-hypofractionated regimen seem appropriate for palliation of unresectable primary breast disease and could become a safe approach for adjuvant treatments. Hypofractionated radiotherapy should be considered for treatment of elderly breast cancer for curative intent, as well as for palliation.

Intrahepatic cholangiocarcinoma is the second most common primary hepatic malignancy and poses a therapeutic challenge owing to its late-stage presentation and treatment-resistant outcomes. Most patients are diagnosed with locally advanced, unresectable disease and are treated with a combination of systemic and local regional therapies. Transarterial radioembolization offers a survival benefit and a favorable side effect profile, with a growing body of evidence to support its use. Herein, we review patient selection and detail outcomes of radioembolization for intrahepatic cholangiocarcinoma, together with mention of competing treatments.

Papillary digital adenocarcinoma (PDA) is a rare eccrine tumor that is most often found on the digits. Few case reports have described PDAs located on atypical sites. It is now accepted that PDAs cannot be distinguished from benign adenomas based on histological features, and it is recommended to excise all of these lesions. Even with excision, recurrence and metastasis rates are high. Only limited genomic analyses have been performed to date, and no driver mutations have been identified. We report a case of a 63-year-old woman with a PDA on the right forearm. Biopsy showed moderate cytologic atypia and mitotic figures. Next-generation DNA sequencing of the tumor showed a BRAFV600E mutation and high tumor mutational burden (5.51 mutations/Mb). This mutation is known for its response to small molecular inhibitors of BRAF and Mitogen-activated protein kinase kinase. Such therapy may be a consideration should our patient develop recurrent unresectable disease.

The diagnosis and management of recurrent rectal cancer is surgically and oncologically challenging. Recurrence usually presents within 1–3 years of treatment for primary tumor, and diagnostic workup should assess pelvic resectability and workup for metastatic disease. Treatment includes neoadjuvant chemotherapy and/or radiotherapy, as well as surgical resection when an R0 resection is feasible. Neoadjuvant chemotherapy and radiotherapy is recommended in chemo/radiotherapy naive patients. Preoperative or intraoperative reirradiation is feasible, but the long term impact on likelihood of R0 resection and survivability is controversial. Chemoradiation may also be used to palliate unresectable disease.

Introduction: Peri-hilar cholangiocarcinoma is an aggressive bile duct cancer. Long-term survival is possible with margin-negative surgery. Historically, unresectable disease was approached with no...

The role of endoscopic ultrasound (EUS) in cholangiocarcinoma (CCA) has grown in recent years due to the suboptimal endoscopic methods in obtaining tissue diagnosis. The current chapter focuses on the role of EUS in the diagnosis and staging of CCA. While EUS-guided fine needle aspiration (FNA) of the primary CCA tumor is strongly discouraged due to risk of tumor seeding, EUS-FNA plays an essential role in evaluating CCA-associated lymphadenopathy and has a significant impact on prognosis and guiding management. Regardless of cross-sectional imaging (unless unresectable disease is identified), EUS can be useful in providing enhanced staging data, primarily via improved nodal assessment. Although primary sclerosing cholangitis and the presence of biliary stents can hinder EUS performance, their impact is greatly minimized by adopting careful examination techniques.

Colorectal cancer (CRC) is a commonly diagnosed malignancy. The prognosis of patients with unresectable, metastatic colorectal cancer (mCRC) is dismal and medical treatment is mainly palliative in nature. Although chemotherapy remains the backbone of treatment, the landscape is changing with the understanding of its heterogeneity and molecular biology. First-line therapy relies on a combination of chemotherapy and targeted therapies, according to clinical patient characteristics and tumor molecular profile. Here we review current evidence from randomized clinical trials for using chemotherapy doublets or triplets, and for the addition of bevacizumab or anti-epidermal growth factor receptor (EGFR) agents. Novel therapies developed for small, selected populations are also discussed.

This subanalysis of an international, multicenter, open-label study assessed efficacy and safety of denosumab in patients with giant cell tumors of bone of the spine including the sacrum. Results suggest denosumab is potentially effective in these patients and the safety profile was consistent with the full study population., Study Design. This was a subanalysis of an international, multicenter, open-label study. Objective. The aim of this study was to assess the efficacy and safety of denosumab in a subset of patients with giant cell tumors of bone (GCTB) of the spine including the sacrum from an international, open-label, single-arm, phase 2 study (ClinicalTrials.gov: NCT00680992). Summary of Background Data. Standard GCTB treatment is surgical removal, either by curettage or resection, combined with intraoperative adjuvant therapy; however, some sites may not be amenable to resection (e.g., skull, spine). Methods. Adults or skeletally mature adolescents with pathologically confirmed GCTB of the spine including the sacrum, and radiologically measurable evidence of active disease, were included. Patients received denosumab (120 mg subcutaneously) once every 4 weeks during the treatment phase, with loading doses on days 8 and 15 of the first cycle. Patients had surgically unsalvageable GCTB (Cohort 1), had planned surgery expected to result in severe morbidity (Cohort 2), or were enrolled from a previous GCTB study (Cohort 3). Results. Overall, 132 patients were included in the safety analysis (103 in Cohort 1, 24 in Cohort 2, and five in Cohort 3); 131 patients were included in the efficacy analysis. Kaplan-Meier estimated probabilities of disease progression or recurrence were 3% (95% confidence interval [CI], 0.0–6.2) at year 1 and 7.4% (95% CI, 2.1–12.7) at years 3 and 5 in Cohort 1, and not estimable in Cohorts 2 and 3. Of 23 patients (Cohort 2) with surgery planned at baseline, 10 (43%) had on-study surgery; of these, one patient had reported disease progression or recurrence after the on-study surgery. Clinical benefit was reported in 83% of patients overall (all cohorts). Conclusion. Results from the analysis suggest that denosumab is potentially effective treatment for patients with GCTB of the spine including the sacrum. The adverse event profile was consistent with the full study population. Level of Evidence: 2

Adenoid cystic carcinoma is a rare disease and characterised by slow but unrelenting local progression and risk of haematogenous metastases. We present a case of locally unresectable disease where PSMA PET/CT provided complementary staging and early treatment response assessment.

Hepatocellular carcinoma is a leading cause of cancer death worldwide. Chemoembolization is the mainstay of therapy for unresectable disease, and also serves as a bridge to transplantation. This chapter reviews patient selection, periprocedural care, and technical requirements for safe and effective performance.

Introduction Hepatic arterial infusion pump (HAIP) therapy for colorectal liver metastases (CRLM) is beneficial in selected patients yet wide acceptance in the oncology community is lacking. Methods A surgeon-led team implemented a HAIP program in 2012. Pumps were placed by laparotomy for CRLM and fluorodeoxyuridine was infused via HAIP every 28 days without systemic chemotherapy supervised by the operating surgeon. Results Sixty patients were treated with HAIP, either in the adjuvant setting after liver resection or ablation of CRLM in 26 (43%) patients or with the unresectable disease in 34 (57%). Perioperative complications occurred in 19 (32%) and pump-specific complications in 14 (23%) that included intrahepatic biliary stricture in one (2%). Time to liver progression was a median 9.2 months (95% CI, 3.1-15.3 months) in unresectable patients and liver recurrence was a median 24.7 months (2.5-46.9 months) in the adjuvant group. Estimated 3-year overall survival from the time of HAIP placement was 64% in the adjuvant group and 37% in the unresectable group. Sarcopenia was prevalent (48%) and was associated with a worse survival (HR 2.4, 95% CI, 1.1-5.0). Conclusion A surgeon-led HAIP program may achieve outcomes on par with those of experienced centers and foster strong relationships between surgical and medical oncologists.

Immune checkpoint inhibitors and BRAF-MEK inhibitors have revolutionized the management and prognosis of patients with metastatic melanoma. However, there is minimal evidence to guide their incorporation into current treatment paradigms for unresectable stage III disease. The era of effective systemic therapies has prompted a discussion about what constitutes unresectable disease. Patients with unresectable stage III disease can experience significant morbidity from their disease and locoregional therapies, and may progress with distant metastases. Despite increasing use of systemic therapies in unresectable stage III disease, further evidence is needed to establish their degree of benefit in this population.

BACKGROUND: Management of neuroendocrine liver metastasis (NELM) in the setting of unresectable disease is poorly defined and the role of debulking remains controversial. The objective of the current study was to define outcomes following non-curative intent liver-directed therapy (debulking) among patients with NELM. METHODS: 612 patients were identified who underwent liver-directed therapy of NELM from a multi-institutional database. Outcomes were stratified according to curative (R0/R1) versus non-curative ≥ 80% debulking (R2). RESULTS: 179 (29.2%) patients had an R2/debulking procedure. Patients undergoing debulking more commonly had more aggressive high-grade tumors (R0/R1: 12.8% vs. R2: 35.0%; P < 0.001) or liver disease burden that was bilateral (R0/R1: 52.8% vs. R2: 75.6%; P < 0.001). After a median follow-up of 51 months, median (R0/R1: not reached vs. R2: 87 months; P < 0.001) and 5-year survival (R0/R1: 85.2% vs. R2: 60.7%; P < 0.001) was higher among patients who underwent an R0/R1 resection compared with patients who underwent a debulking operation. Among patients with ≥50% NELM liver involvement, median and 5-year survival following debulking was 55.4 months and 40.6%, respectively. CONCLUSION: Debulking operations for NELM provided reasonable long-term survival. Hepatic debulking for patients with NELM is a reasonable therapeutic option for patients with grossly unresectable disease that may provide a survival benefit. info:eu-repo/semantics/publishedVersion

Primary and secondary malignancies of the liver and pancreas result in significant morbidity and mortality, with increasing incidence and increasing demands on health services worldwide. Surgery is the only curative single modality of treatment and remains the gold standard. Unfortunately, up to 80% of the patients present with unresectable disease, and so, alternative efficacious local and systemic treatments are needed. Technologic advances in radiotherapy over recent decades have meant that precision high-dose treatment with stereotactic body radiotherapy (SBRT) has emerged as a viable cost-effective outpatient-based treatment in the management of these difficult to treat abdominal malignancies. This article reviews the current indications for SBRT in these settings, comparing it with other treatments including surgery, chemotherapy, radiofrequency ablation, and trans-arterial chemoembolisation. We also review the current use of abdominal SBRT and future projections in the Irish healthcare setting.

Aim of the study Recent advances in chemotherapy have increasingly enabled conversion surgery (CS) in patients with initially unresectable pancreatic cancer (PC), but patient selection remains controversial. We examined the characteristics of patients who would benefit from this procedure. Material and methods The clinical and pathological data of 38 patients with unresectable PC, who underwent CS after a favourable response to chemo(radio)therapy at our institute, were investigated. Univariate and multivariate analyses were performed to identify predictors for overall survival (OS). Several inflammation-based scores, such as the modified Glasgow prognostic score (mGPS), were also evaluated. Results The patients included 13 with locally advanced disease and 25 with metastatic disease. After non-surgical treatment with a median duration of six months, 27 patients (71%) underwent R0/1 resection, and the remainder underwent R2 resection. The two-year and five-year OS from the initial treatment for all patients were 64% and 29%, respectively, and the median survival was 29.1 months. Univariate analysis showed that age < 62 years, preoperative CA19-9 decrease rate ≥ 89%, preoperative mGPS-0, and R0/1 resection were related to a favourable OS. R0/1 resection and mGPS-0 were independent prognostic factors according to multivariate analysis. Conclusions Preoperative mGPS is a potential predictor of survival and can aid selection of patients for whom CS could yield promising prognosis for initially unresectable PC.

The use of heated intraperitoneal chemotherapy (HIPEC) in conjunction with cytoreductive surgery has been gaining increasing traction in treating gastric adenocarcinoma with metastasis to the peritoneum in recent years. The addition of laparoscopic HIPEC (LS-HIPEC) to these treatment algorithms has increased the flexibility and adaptability of HIPEC integrating into treatment sequencing, allowing for iterative protocols of LS-HIPEC prior to cytoreduction as neoadjuvant treatment, as well as in the palliation of patients with unresectable disease and uncontrolled ascites. As the use of HIPEC in gastric adenocarcinoma continues to be refined, LS-HIPEC algorithms should continue to be considered and utilized both in curative treatment algorithms as well as in patients in the palliative setting. Given that LS-HIPEC remains a relatively nascent treatment modality, we advocate for its use in the setting of a clinical trial when feasible.

Objectives: Our study evaluates survival of women with early-stage ovarian cancer treated with neoadjuvant chemotherapy (NAC) vs primary debulking surgery (PDS). Methods: We used the 2004-2015 NCDB to identify women with early ovarian cancer treated with multiagent chemotherapy and appropriate surgery. Logistic regression was used to identify predictors of NAC. Overall survival estimates were compared using Kaplan-Meier analysis and Cox proportional hazards regression models were used to examine variables. Results: In total, 14,627 women were included. The majority (96%) underwent PDS while (4%) underwent NAC. Median survival times were 40 months (95% CI [37.190-47.280], P Download : Download high-res image (124KB) Download : Download full-size image Conclusions: Women treated with neoadjuvant chemotherapy (NAC) had worse overall and 5-year survival. This finding agrees with the accepted convention of reserving NAC for women with advanced, unresectable disease.

e16217 Background: The vast majority of pancreatic ductal adenocarcinoma (PDAC) patients have unresectable disease at diagnosis, with only about 20% presenting with either resectable or borderline resectable tumors and who may receive adjuvant with or without neo-adjuvant treatment with surgery. This study seeks to characterize these treatment patterns in the real-world setting. Methods: This was a retrospective observational study to evaluate adjuvant treatment of PDAC patients, with or without neo-adjuvant treatment in the U.S. Patients with at least two medical claims with a primary diagnosis for PDAC between 2016 to 2019 were identified in the Truven MarketScan administrative claims database. A surgical resection within 3 months of any primary PDAC coded medical encounter was the index event, with patients required to be continuously enrolled for at least 3 months before and 6 months after the surgery. Patient demographics and treatment patterns (chemotherapy, radiotherapy, and chemoradiation) were evaluated over the pre-index (3 months) and post-index (3 and 6 months) observation windows. Neo-adjuvant and adjuvant treatment patterns were reported for the overall population and also stratified by age and sex. Results: 737 patients met the selection criteria with a majority (n=520, 71%) being

Metastatic liver disease is a major cause of cancer-related morbidity and mortality. Surgical resection is considered the only curative treatment, yet only a minority is eligible. Patients who present with unresectable disease are treated with systemic agents and/or locoregional therapies. The latter include thermal ablation and catheter-based transarterial interventions. Thermal ablation is reserved for those with limited tumor burden. It is used to downstage the disease to enable curative surgical resection, as an adjunct to surgery, or in select patients it is potentially curative. Transarterial therapies are indicated in those with more diffuse disease. The goals of care are to palliate symptoms and prolong survival. The indications and supporting data for thermal ablation and transarterial interventions are reviewed, technical and tumor factors that need to be considered prior to intervention are outlined, and finally several cases are presented.

Since the first report in 1990 by Dohomoto et al., endoluminal stenting of the colorectum has become a viable alternative to surgery. For patients with unresectable disease, stent implantation can be considered, avoiding the need for colostomy and has been associated with a better quality of life. The long-term outcomes of palliative stenting has shown favorable results. Emergency surgery in patients with colonic obstruction is associated with significant morbidity and mortality rates. Stenting as bridge to surgery is now an alternative to emergency surgery despite the uncertainity of its long-term oncologic safety. Colonic stenting has been used in benign colonic obstructions but the data on long-term outcomes remains limited. The appropriate decision for stent or surgery in the setting of acute colonic obstruction requires a structured approach.

Despite its low incidence in the general population, pancreatic cancer is one of the leading causes of cancer-related mortality. Survival greatly depends on operability, but most patients present with unresectable disease. Therefore, there is great interest in the early detection of pancreatic cancer and its precursor lesions by surveillance. Worldwide, several programs have been initiated for individuals at high risk for pancreatic cancer. Their first results suggest that surveillance in high-risk individuals is feasible, but their effectiveness in decreasing mortality remains to be proven. This review will discuss which individuals are eligible for surveillance, which lesions are aimed to be detected, and which surveillance modalities are being used in current clinical practice. Furthermore, it addresses the management of abnormalities found during surveillance and topics for future research.

Introduction: Pancreatic cancer is a leading cause of cancer-related death. Its diagnosis is often delayed and patients are frequently found to have unresectable disease. Patients diagnosed with new-onset diabetes have an 8-fold risk of harboring pancreatic cancer. Adrenomedullin has been claimed to mediate diabetes in pancreatic cancer. New screening tools are needed to develop an early diagnosis protocol. Methods: Patients aged 45-75 years within 2 years of first fulfilling the ADA criteria for diabetes will be prospectively enrolled in this study. Sepsis, renal failure, microangiopathy, pregnancy, acute heart failure and previous malignancies will be considered as exclusion criteria. Results: 440 patients diagnosed with new-onset diabetes will be enrolled and divided into 2 groups: one with high adrenomedullin levels and one with low adrenomedullin levels. Patients will undergo 3 years’ follow-up to detect pancreatic cancer development. Conclusions: Identifying a marker for pancreatic cancer among high-risk patients such as new-onset diabetics might lead to the identification of a subpopulation needing to be screened in order to enable early diagnosis and treatment of a highly lethal tumor. Trial registration: This trial was registered at ClinicalTrials.gov on May 25, 2015 under registration number NCT02456051.

Introduction: The liver is the most common metastatic site in colorectal cancer with more than half the patients developing a liver metastasis either at the time of their diagnosis (synchronous) or later (metachronous). Surgical resection remains the principal curative approach that offers significant survival improvements. However, upfront surgery is only possible in about 10-20% of patients at the time of diagnosis, making the consideration of other treatment modalities essential. Areas covered: In this review, the authors provide an overview of the standard approaches for the initial management of patients with colorectal cancer with liver metastases. They then provide an up-to-date discussion of first-line systemic chemotherapy/targeted therapy options in the contexts of initially resectable and unresectable disease and review toxicities and complications following these options. Expert opinion: Advances in chemotherapeutic agents and biological targeted therapies have improved the prognosis of colorectal cancer with liver metastases. However, there is still no 'single best approach', making further trials necessary to provide more evidence.

Immunotherapy has revolutionized the treatment of melanoma, with implications for the surgical management of this disease. Surgeons must be aware of the impact of various immunotherapies on patients with resectable and unresectable disease, and how surgical decision-making should progress as a result. We expect that current and developing immunotherapies will increase surgeon involvement for resection of metastatic melanoma, whether for tumor harvests to generate autologous lymphocytes or for consolidating control of disease beyond what immunotherapies alone can achieve. Despite remarkable advancements in the field, significant work is needed to optimize the immuno-modulation that targets cancers while minimizing toxicity for patients.

espanolEl colangiocarcinoma es una neoplasia maligna, relativamente rara que surge del epitelio de los conductos biliares. Se puede clasificar segun su distribucion anatomica como intrahepatico o extrahepatico. Las variaciones geograficas en la incidencia del colangiocarcinoma estan relacionadas con variaciones en los factores de riesgo, entre los principales estan la hepatitis viral, cirrosis, colangitis esclerosante primaria y colelitiasis.A pesar de las diferencias en la ubicacion del colangiocarcinoma, este se asocia con un mal pronostico y es la reseccion quirurgica quien ofrece la mejor posibilidad de curacion. La resistencia terapeutica se ve influenciada por el rico microambiente tumoral y la heterogeneidad genetica caracteristica del colangiocarcinoma. Aquellos pacientes con enfermedad irresecable siguen siendo considerados como incurables. EnglishCholangiocarcinoma is a relatively rare malignant neoplasm that arises from the bile duct epithelium. It can be classified according to its anatomical distribution as intrahepatic or extrahepatic. Geographical variations in the incidence of cholangiocarcinoma are related to variations in risk factors, the main ones being viral hepatitis, cirrhosis, primary sclerosing cholangitis and cholelithiasis.Despite the differences in the location of cholangiocarcinoma, it is associated with a poor prognosis and it is surgical resection that offers the best chance of cure. Therapeutic resistance is influenced by the rich tumor microenvironment and genetic heterogeneity characteristic of cholangiocarcinoma. Those patients with unresectable disease are still considered incurable.

284 Background: Esophagogastric cancer (EGC) carries a heavy mortality burden owing largely to high rates of unresectable disease at diagnosis. Among patients not undergoing curative-intent therapy, access to care may vary. We examined the geographic distribution of care delivery and survival across a jurisdiction, and its relationship with distance to cancer centres (CCs), for non-curative EGC. Methods: We conducted a population-based analysis of adults with non-curative EGC from 2005-2017 using linked administrative healthcare datasets in Ontario, Canada. Outcomes were medical oncology consultation, receipt of chemotherapy, and overall survival (OS). We used geographic information system analysis to map locations of CCs and outcomes across census divisions. Regions of discordance between care use and OS were identified with bivariate choropleth maps. Multivariable modified Poisson models assessed the relationship between distance to the nearest CC and outcomes, adjusting for demographic, clinical, and socioeconomic factors. Results: Of 10,228 patients surviving a median of 5.1 months (IQR: 2.0-12.0), 68.6% had medical oncology consultation and 32.2% received chemotherapy. Regions of comparable OS and care delivery were clustered throughout the province. CCs were distributed unevenly, with higher levels in Southern Ontario. Higher-level CCs clustered in regions with higher rates of consultation, chemotherapy use, and OS. Each increment in distance from location of residence to the nearest CC (11-50, 51-100, and ≥101 km) was associated with lower likelihood of seeing medical oncology and receiving chemotherapy, and inferior OS, compared to ≤10 km. Conclusions: A third of patients with non-curative EGC did not see medical oncology, and the majority did not receive chemotherapy. Care delivery and OS exhibited high geographic variability. Location of residence influenced access to care and OS, with inferior outcomes for those living further from a CC. These findings are important for designing interventions and policies to reduce disparities in access to care and outcomes for non-curative EGC.

690 Background: Downstaging of pancreatic adenocarcinoma in patients presenting with nonmetastatic, unresectable disease has proven to be associated with improved clinical outcomes. Efforts at rescuing these patients to become surgical candidates are commonly attempted with a combination of systemic and radiation strategies. In this study, we aimed to determine tumor downsizing in patients that underwent neoadjuvant systemic therapy followed by a curative-intended surgical resection. Methods: A retrospective review of consecutive patients that underwent surgical resection for pancreatic adenocarcinoma following a course of neoadjuvant therapy was performed. Basic demographics, endoscopic ultrasound (EUS) findings, chemotherapy regimens and duration, rates of radiotherapy, type of surgical procedure and pathologic results were recorded. Tumor response to neoadjuvant therapy was established by correlating EUS- to pathologic tumor dimensions. Analysis of the data was done using Mann-Whitney U test, Pearson correlation and Chi-square when indicated. Results: A total of 97 patients were analyzed; 40 underwent neoadjuvant chemotherapy (13 patients also received concurrent radiation therapy). In those 57 patients that were resected upfront, EUS tended to underestimate tumor sizes significantly compared to pathologic dimensions, with an average difference between dimensions of 0.66 cm (p = 0.0004). Within the group treated with neoadjuvant chemotherapy, 90% of patients had downsizing at an average of 8% of tumor size. There were no differences in rates of tumor downsizing between FOLFIRINOX or Gemcitabine/Nac-paclitaxel treated patients. In addition, there were no correlations in margin status (R0) based on chemotherapy used, with both regimens achieving a similar rate of R0 resections (mean 61%). The type of chemotherapy regimen used did not affect the ratio of positive lymph nodes harvested. Conclusions: In patients that present with borderline resectable pancreatic adenocarcinoma, a course of neoadjuvant therapy results in tumor downsizing in a significant number allowing for margin negative resections. These results were seen regardless of the chemotherapeutic regimens utilized.

For all of the optimism that immunotherapy has engendered, the flip side is that 7/10 patients with susceptible tumor types do not respond, while in nonsusceptible tumor types the response rates are significantly lower. In contradiction of the current orthodoxy against surgery in the setting of unresectable disease, we present 3 examples of immunotherapy-treated patients with widespread recurrence who experienced dramatic clinical improvement following debulking/metastasectomy. Taken together with examples from the literature that correlate longer survival with surgical intervention during treatment with immunotherapy, these 3 cases suggest that a new paradigm involving a wider role for surgery in the management of these patients should be explored. Possible mechanisms by which surgery may synergize with immunotherapy and improve outcomes are also discussed.

The aim was to evaluate the outcome of treatment-naive patients with synchronous metastatic rectal cancer after chemotherapy with FOLFOXIRI followed by local therapeutic procedures of all tumor lesions as complete as possible. We reviewed data of 30 patients with synchronous distant metastatic rectal cancer who underwent chemotherapy with FOLFOXIRI and subsequent local therapy in our institution. Median follow-up was 28 months (range: 8; 74). Cumulative overall survival (OS) and progression-free survival (PFS) was 93.3, 76.9, 55.6% and 46.2, 29.7, 29.7% after 1, 2, 4 years. Non-response to chemotherapy with FOLFOXIRI was associated with a highly significant decreased OS (p

Pancreatic ductal adenocarcinoma (PDAC) is a relatively common malignancy that carries an overall poor prognosis, with five-year survival below 10%. Despite ongoing research, surgical resection remains the only potentially curative treatment. Therefore, accurate identification of those patients who would benefit from surgical resection is of paramount importance. High-quality imaging and image interpretation is central to this process. Radiology helps in the determination of whether patients are resectable, borderline resectable, or unresectable and guides treatment planning.

To determine oncological and neuromorbidity outcomes in patients with advanced head and neck cancer (stage IVB) requiring sacrifice and reconstruction of the carotid artery.Case series with chart review.Tertiary care referral center.Overall, 51 patients underwent carotid artery sacrifice during surgical treatment of the neck, in both the primary and salvage setting. All patients underwent autogenous in-line carotid artery bypass grafting with either saphenous vein or the deep femoral vein in conjunction with vascular surgery. In all, the study included 39 males and 12 female subjects, with age ranging from 39 to 82 (mean, 62.7).Two patients (3.9%) had a cerebral vascular accident in the immediate postoperative period. The remaining 49 patients (96%) had no neurologic sequela. Serial ultrasonic evaluation revealed 4 patients with intra-luminal thrombus within the site of reconstruction. Perioperative mortality occurred in a single patient. Disease-related mortality occurred in 9.8% (5) of patients, with an overall 2-year survival of 82%.We presently report the largest series of surgical treatment for advanced head and neck cancer with carotid artery involvement. We document an overall 2-year survival of 82% in the setting of low perioperative neuromorbidity and mortality rates. We therefore consider carotid artery sacrifice and autogenous vein graft reconstruction in the absence of distant metastatic disease as a viable treatment option for what was once thought to be a palliative procedure.

In-transit melanoma is an uncommon pattern of recurrence, but presents unique management challenges and opportunities for treatment. The clinical presentation usually involves from 1 to more than 100 small subcutaneous or cutaneous nodules, ranging from submillimeter to multiple centimeters in diameter. Regional chemotherapy techniques are a mainstay of treatment of patients without systemic disease spread. Future applications of regional therapy are likely to involve combination therapy with cytotoxic agents and novel immune modulators. Regional therapy provides distinct opportunities for the treatment of unresectable disease, and offers a unique platform for investigation of novel therapeutics in early-stage clinical trials.

When it comes to cancer treatment, few have been as difficult as renal cell carcinoma (RCC). Many patients present with advanced or unresectable disease, and up to 30% of patients who have initiall...

Background: Most patients with cholangiocarcinoma (CCA) have unresectable disease. Endoscopic bile duct drainage is one of the major objectives of palliation of obstructive jaundice. Methods/Results: Stent implantation using endoscopic retrograde cholangiography is considered to be the standard technique. Unilateral versus bilateral stenting is associated with different advantages and disadvantages; however, a standard approach is still not defined. As there are various kinds of stents, there is an ongoing discussion on which stent to use in which situation. Palliation of obstructive jaundice can be augmented through the use of photodynamic therapy (PDT). Studies have shown a prolonged survival for the combinations of PDT and different stent applications as well as combinations of PDT and additional systemic chemotherapy. Conclusion: More well-designed studies are needed to better evaluate and standardize endoscopic treatment of unresectable CCA.

Colorectal cancer is a frequent neoplasia, with considerable physical and psychological symptom burden and mortality. The management of stage IV patients has significantly changed over the last decades and is nowadays interdisciplinary, allowing an important increase in survival and in quality of life. The limited possibilities available for the treatment of colorectal metastases are no longer the rule. Therefore, to provide optimal outcomes for patients with liver metastases, it is imperative to consider all treatment options available, based on each patient’s comorbidities, tumor extent, preferences, and available technical and professional resources. Nevertheless, it must be acknowledged that there are unique aspects for decision-making that involve clinical, ethical, and communication aspects.

This article aims at analyzing the published literature concerning the treatment of patients with gastric cancer and distant nodal metastases, actually considered metastatic disease. A systematic search was undertaken using Medline, Embase, Cochrane and Web-of-Science libraries. No specific restriction on year of publication was used; preference was given to English papers. Both clinical series and literature reviews were selected. Only 11 papers address the issue of surgery for nodal basins outside the D2 dissection area. From these papers, in selected cases extended surgery may prove useful in prolonging survival, when a comprehensive therapeutic pathway including chemotherapy is scheduled. In conclusion, in presence of nodal metastases outside the loco-regional nodes, surgery may be considered for metastatic nodes in stations 13 and 16, in selected cases.

Radiation therapy plays a large role in many gynecologic cancers. In cervical cancer, it can be used as curative treatment, often in the form of external beam radiation therapy (EBRT), followed by brachytherapy. For endometrial, vulvar, and vaginal cancers, often radiation can be used adjuvantly after surgery, but for patients with unresectable disease, or gross disease left in lymph nodes or elsewhere in the pelvis after surgery, it can also be used with definitive intent.

Surgical resection is the only curative modality for colorectal liver metastases (CLM), and 5-year overall survival after resection is about 40%. Nonresectable CLM is not curable and 5-year overall survival is currently about 10%. Before 1995, several liver transplantations for CLMs were performed, but outcome was poor (5-year survival rate: 18%). Consequently, CLMs were considered a contraindication to liver transplantation. Since then, the survival rate after liver transplantation in general has improved by almost 30%. In a prospective pilot study of liver transplantation for nonresectable CLM, a 5-year overall survival rate of 60% was demonstrated; however, 19 of 21 patients experienced recurrence of disease. Patient selection and selection criteria is of critical importance to achieve good results. The access to liver grafts is the main limiting factor, and novel developments are needed if liver transplantation for selected cases of CLM is going to be a clinical reality. By review of the current and ongoing research in this field, the potential role for liver transplantation as one of several treatment modalities for CLM is discussed.

Background and study aims It is unclear to what extent EUS influences the surgical management of patients with pancreatic adenocarcinoma. This systematic review sought to determine if EUS evaluation improves the identification of unresectable disease among adults with pancreatic adenocarcinoma. Patients and methods We searched MEDLINE, EMBASE, bibliographies of included articles and conference proceedings for studies reporting original data regarding surgical management and/or survival among patients with pancreatic adenocarcinoma, from inception to January 7th 2017. Our main outcome was the incremental benefit of EUS for the identification of unresectable disease (IBEUS). The pooled IBEUS were calculated using random effects models. Heterogeneity was explored using stratified meta-analysis and meta-regression. Results Among 4,903 citations identified, we included 8 cohort studies (study periods from 1992 to 2007) that examined the identification of unresectable disease (n = 795). Random effects meta-analysis suggested that EUS alone identified unresectable disease in 19% of patients (95% confidence interval [CI], 10-33%). Among those studies that considered portal or mesenteric vein invasion as potentially resectable, EUS alone was able to identify unresectable disease in 14% of patients (95% CI 8-24%) after a CT scan was performed. Limitations The majority of the included studies were retrospective. Conclusions EUS evaluation is associated with increased identification of unresectable disease among adults with pancreatic adenocarcinoma.

Background This study investigates whether there has been any survival improvement for hepatocellular carcinoma patients with resectable and unresectable lung metastases over time. Methods The data of 280 hepatocellular carcinoma patients who developed metachronous lung metastases after hepatectomy with curative intent were analysed. Overall survival was compared in patients with resectable and unresectable lung metastases and in different periods (Era I: 1989–1995, Era II: 1996–2010). Results The median overall survival of patients with unresectable and resectable diseases was 7.46 and 40.36 months, respectively (P < 0.0001). In Era I, the median overall survival of patients with unresectable and resectable diseases was 5.59 and 43.15 months, respectively (P < 0.0001). The corresponding figures in Era II were 8.38 and 32.90 months (P < 0.0001). The overall survival of patients with resectable disease did not differ significantly in the two eras but there was a significant improvement in survival of patients with unresectable disease in Era II. Their 1-year, 3-year and 5-year survival rates in Era I versus Era II were 11.1% versus 38.4%, 5.6% versus 9.1% and 2.8% versus 3.5%, respectively (P = 0.041). The corresponding figures for their counterparts in the resectable group were 90% versus 85.8%, 80% versus 45.9% and 40% versus 29.5%, respectively (P = 0.443). Conclusions Patients with resectable lung metastases had better overall survival than those with unresectable lung metastases. Notably, patients with unresectable lung metastases had significant improvement in survival over the years.

Use of colorectal stents has increased dramatically over the last decades. Colorectal stents offer an alternative way to relieve fatal intestinal obstruction and can take place of emergency surgery, which associated with significant morbidity and mortality and a high incidence of stoma creation, to elective resection. Although there remain a few concerns regarding the use of stents as a bridge to surgical resection, use of self-expandable metallic stents for palliation in patients with unresectable disease has come to be generally accepted. Advantages of colorectal stents include acute restoration of luminal patency and allowance of time for proper staging and surgical optimization, and the well-known disadvantages are procedure-related complications including perforation, migration, and stent failure. General indications, procedures, and clinical outcomes as well as recent evidences regarding the use of colorectal stents will be discussed in this review.

The most frequent solid organ involved in metastatic neuroendocrine tumors (NET) is the liver. Hepatic metastases occur during the lifetime of 46% to 93% of patients with NETs. Intra-arterial embolotherapies are palliative and should be used for patients with unresectable disease not amenable to resection or ablation. The most widely accepted indications for liver embololization for NET metastases are progression of unresectable hepatic metastases threatening liver function and palliation of hormone-related symptoms uncontrolled by somatostatin analogues. This article will discuss patient selection and administration of all embolotherapies currently used for palliation of neuroendocrine liver metastases.

413 Background: Fibrolamellar carcinoma (FLC) is a very rare liver tumor, comprising only 1% of all primary liver tumors in the United Sates. There is no standard of care for unresectable disease. Current practices are based on small retrospective studies and case series. We aim to analyze the clinicopathologic factors and treatment modalities affecting overall survival (OS) in FLC. Methods: Using the National Cancer Data Base (NCDB), we identified 496 patients diagnosed with FLC between 2004 and 2015. Simple descriptive statistics were created for all covariates. Survival data was available on 461 patients. Kaplan Meier Survival analysis was used for unadjusted results, and Cox proportional hazards model was used for multivariable analysis. The objective of the study is to identify predictors of survival in FLC. Results: The median age at diagnosis was 32 (range 18-90) years. Fifty-six percent were males. Stage distribution included 114 (31.2%), 43 (11.8%), 89 (24.3%) and 120 (32.8%) patients for stages I, II, III and IV, respectively. Median follow-up was 24 months. Surgery of the primary site was performed on 282 (56.9%) of patients, 146 (51.2%) of which had regional lymph node dissection. Seventy (47.9%) patients had pN+ disease. Among patients with available serum alpha fetoprotein (AFP) data, 146 (42.5%) had abnormal AFP levels (> 20 ng/mL). Median OS by stage were 78.5, 87.2, 18.6, and 10.6 months for stages I, II, III, and IV, respectively. Multivariate analysis showed that age (HR 1.01, p < 0.0001), pN+ (HR 2.31, p = 0.0003), and abnormal AFP (HR 1.69, p = 0.0003) were negative predictors of survival. Among metastatic patients, 57 (11.4%) had metastatectomy. Metastatectomy improved overall survival in stage IV FLC, HR 0.51 (95% CI 0.29-0.89). Conclusions: Independent predictors of decreased OS in patients with FLC include age, pN+ and abnormal AFP. Metastatectomy improved OS. FLC is a rare disease entity that warrants further investigations to better delineate optimal treatment approaches.

In 2017, results from phase III trials demonstrated the impressive safety and efficacy of adjuvant targeted and immune therapies in patients with resectable stage III–IV melanoma, and raised questions about the surgical management of patients with microscopic sentinel-lymph-node metastases. For patients with unresectable disease, new overall survival data added to the debate about the relative benefits of single-agent anti-PD-1 versus combined anti-PD-1 and anti-CTLA-4 immunotherapy.

Immunotherapies and BRAF and MEK inhibitors have dramatically improved outcomes in advanced melanoma. The availability of these novel approaches has necessitated changes to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). The NCCN Guidelines feature algorithms that aid clinicians in selecting initial therapy, which now includes anti-programmed death protein receptor-1 PD-1 inhibitors among the recommended systemic therapy options for patients with metastatic or unresectable disease.

The surgical palliation of pancreatic cancer remains an important component of the treatment of this disease. The introduction of a new aggressive and effective chemotherapy regimen (FOLFIRINOX), interdisciplinary palliative care, and minimally invasive approaches for providing palliation are all factors that expand the role of the surgeon in the care of patients with unresectable disease. Currently, the role of the surgeon in the palliation of pancreatic cancer is (1) to identify patients with incurable disease (either preoperatively or intraoperatively), (2) to determine the optimal palliative technique to optimize results and preserve resources, and (3) to perform palliation of symptoms with low morbidity and mortality. The 3 most common symptoms of pancreatic cancer requiring surgical palliation are obstructive jaundice, gastric outlet obstruction, and tumor-associated pain. It is important that the surgeon recognizes the full range of surgical and nonoperative techniques available and contributes to the decision making as to the most appropriate method for each individual patient.

In the last module of this consensus, controversial topics were discussed. Management of the disease after progression during first line chemotherapy was the first discussion. Next, the benefits of liver resection in the presence of extra-hepatic disease were debated, as soon as, the best sequence of treatment. Conversion chemotherapy in the presence of unresectable liver disease was also discussed in this module. Lastly, the approach to the unresectable disease was also discussed, focusing in the best chemotherapy regimens and hole of chemo-embolization. RESUMO Neste último módulo do consenso, abordou-se alguns temas controversos. O primeiro tópico discutido foi o manejo da doença após progressão na primeira linha de quimioterapia, com foco em se ainda haveria indicação cirúrgica neste cenário. A seguir, o painel debruçou-se sobre as situações de ressecção da doença hepática na presença de doença extra-hepática, assim como, qual a melhor sequência de tratamento. O tratamento de conversão para doença inicialmente irressecável também foi abordado neste módulo, incluindo as importantes definições de quando se pode esperar que a doença se torne ressecável e quais esquemas terapêuticos seriam mais efetivos à luz dos conhecimentos atuais sobre a biologia tumoral e taxas de resposta objetiva. Por último, o tratamento da doença não passível de ressecção foi discutida, focando-se nos melhores esquemas a serem empregados e seu sequenciamento, bem como o papel da quimioembolização no manejo destes pacientes.