Targeted immunotherapy for solid gastrointestinal malignancies is challenging due to a lack of identified tumor antigens. Therefore, a strategy that supports and expands tumor infiltrating lymphocytes in the tumor microenvironment may allow these tumor-reactive T-cells to incite an antitumor response. Gene expression analysis of colon metastases has identified specific immunotherapeutic targets for this malignancy.

Introduction

Introduction Laparoscopic adrenalectomy (LA) may be associated with reduction in postoperative pain, morbidity, length of stay, and cost compared to open adrenalectomy, and, as a result, has become a preferred approach for benign tumors. Though recent series have reported safety and oncologic non-inferiority with a minimally invasive approach to malignant and metastatic adrenal tumors, relative contraindications to LA include malignancy, large size, and invasion or abutment of vital structures.

Methods/results

We demonstrate techniques to perform LA in an obese patient with a large ([6 cm) solitary breast metastasis to the right adrenal gland that was adherent to the liver, inferior vena cava (IVC), and right renal vein. The tumor was growing behind the infrahepatic IVC and was abutting the confluence of the renal vein/IVC. The patient was monitored on systemic treatment with no new sites of disease and after achieving a maximal response to neoadjuvant treatment. Laparoscopic techniques to safely approach adrenal tumors adherent to the liver, IVC, and renal vein are stepwise demonstrated, including appropriate patient positioning and port site selection. The tumor was excised with negative margins, and the patient was discharged on postoperative day 1 with minimal pain medication and tolerating a regular diet.

Conclusion

Though malignancy is a relative contraindication to LA, even large right-sided adrenal tumors abutting the liver and growing behind the IVC can be safely approached while adhering to oncologic principles, as is demonstrated in this video.

Immunotherapy has changed the environment of cancer treatment by providing new and efficacious therapy options for many solid and hematologic malignancies. Although not a new field of oncology, immunotherapy has quickly developed into one of the most flourishing fields in medicine. In this review article, we explore key discoveries which helped to shape our current understanding of the immune system's role in neoplasms. Many landmark developments include the advancements in checkpoint inhibitors, monoclonal antibodies, CAR-T cells and anti-cancer vaccines. We also explore the drawbacks and efficacy of various categories of immunotherapy. Ongoing investigations within immunotherapy, such as the gut microbiome, combining checkpoint inhibitors and gene sequencing, continue to personalize treatments for cancer patients, providing exciting and endless possibilities for the future.

Modern series report a prevalence of pancreatic cysts in the general population of up to 50% in prospective studies. Of these, about half will be pancreatic cystic neoplasms (PCNs) that have varying degrees of malignant potential. Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are the most common PCNs and are known predecessors of pancreatic adenocarcinoma. Critically, they are one of the only radiographically identifiable precursors of pancreatic cancer and thus provide an opportunity for early cancer detection and surgical resection with curative intent. The combination of high prevalence and potential for malignant degeneration underscore the relevance of discussing the best management of IPMNs and improving the existing standard of care. Landmark data on IPMN prevalence, guidelines, surveillance, biomarkers, and immune landscape are highlighted.

Background

The use of chemotherapy among patients with stage II colon cancer is controversial. We aimed to define the utilization and factors associated with the receipt of chemotherapy and the impact of chemotherapy on long-term prognosis among a large, multiinstitutional cohort of patients.

Materials and methods

We identified 876 patients who underwent resection for stage II colon cancer between 2004 and 2013 at one of seven participating institutions. Overall survival (OS) and recurrence-free survival (RFS) time was calculated from the date of the index procedure to the date of death.

Results

A total of 163 patients (18.6%) received adjuvant chemotherapy and this utilization decreased over time (P = 0.003). Younger age (P < 0.001), margin positivity (odds ratio [OR], 12.16; 95% confidence interval [CI]: 2.57-57.52; P = 0.002), and the presence of perineural invasion (OR, 1.24; 95% CI: 1.07-1.44; P = 0.005) increased the likelihood of receiving chemotherapy. Receipt of chemotherapy was associated with improved median OS and RFS. After controlling for all factors, the addition of oxaliplatin to 5-fluorouracil did not affect survival, and there was no difference in OS (hazard ratio [HR], 0.74; 95% CI: 0.27-2.06; P = 0.57) or RFS (HR, 0.71; 95% CI: 0.32-1.58; P = 0.88) with adjuvant treatment, including for patients with high-risk features (OS-HR, 0.63; 95% CI: 0.33-1.19; P = 0.15; RFS-HR, 0.77; 95% CI: 0.32-1.86; P = 0.56).

Conclusions

The utilization of chemotherapy has declined over time after resection for stage II colon cancer. Chemotherapy was not independently associated with improved OS or RFS in this study group, including in patients with high-risk features. Future prospective studies should strive to identify the subset of stage II colon cancer patients that will benefit the most from the addition of adjuvant chemotherapy.

Rose Bengal (RB) is a red synthetic dye that was initially used in the garment industry and has been used safely for decades as a corneal stain by ophthalmologists. Antineoplastic properties of RB have also been observed, though the mechanism of action remained to be elucidated. Recently, interest in RB as a therapeutic cancer treatment has increased due to significant anti-tumor responses with direct tumor injection in human clinical trials for metastatic melanoma. In these patients, there has been the implication that RB may mount a T-cell mediated anti-tumor response and impart antigen-specific responses in distant bystander lesions. This article serves to evaluate the potential of intralesional rose bengal to stimulate T-cell mediated anti-tumor responses in in-vitro, pre-clinical, and clinical studies.

Introduction

Minimally invasive adrenalectomy may be associated with reduction in postoperative pain, morbidity, and length of stay and, as a result, has become a preferred approach for many adrenal tumors. Left-sided adrenal tumors, however, are particularly challenging to address in the morbidly obese patient due to difficulties in maintaining exposure and dissection. The robotic platform offers instruments with greater degrees of freedom that aid in retraction and dissection, especially of the adrenal vein, but fixed patient positioning and the large distance needed between patient ports to avoid arm collisions can be restrictive in patients with a large amount of retroperitoneal fat and small working space.

Methods/results

We demonstrate robotic left adrenalectomy (RLA) in a consecutive series of patients with a mean weight of 99 kg and mean BMI of 36. Techniques to safely and efficiently perform RLA in obese patients are stepwise demonstrated, including (1) Patient positioning, (2) Management of the pannus, (3) Customized port placement, (4) Medial retraction of the pancreas, (5) Finding the left adrenal vein, and (6) Management of bleeding. Intraoperative videos from multiple patients also show surgical pitfalls, examples of poor port placement, arm collisions, alternative approaches to the vein, and techniques to control unexpected bleeding. All patients in the series underwent successful RLA with negative margins, no major intra- or postoperative complications, and discharge on POD 1-2.

Conclusion

Though poor exposure due to patient body habitus is a relative contraindication, even large left-sided adrenal tumors can be safely approached robotically while adhering to oncologic principles, as is demonstrated in this video.

Background

T-cell infiltration in primary colon tumors is associated with improved patient survival. Preliminary data supports a similar association in colorectal liver metastases (CRLM), and we previously identified increased CRLM expression of the immunostimulatory cytokine LIGHT (TNFSF14) to be related to improved patient prognosis. Therefore, mechanisms to augment the T-cell response in CRLM may be a promising treatment modality, however, the tumor immune microenvironment and LIGHT expression in CRLM remains to be characterized.

Methods

Utilizing a syngeneic and immunocompetent model of CRLM, the immune microenvironment was characterized for lymphocyte phenotype, function, and location utilizing flow cytometry, immunoassays, and immunofluorescence microscopy.

Results

CD3+ and CD4+ lymphocytes were decreased, and CD8+ cells were increased in CRLM compared to control liver. When present, greater populations of tumor infiltrating lymphocytes (TIL) were found peritumoral than intratumoral. The TIL expressed significantly higher levels of CD69 and CD107a, but lower levels of LIGHT. Cytokine expression profiles revealed increased levels of the T-helper 1 (Th1) cytokines IFN gamma, IL-12, IL-1b, and IL-8 in CRLM compared to control liver tissue. There was no difference in T-helper 2 (Th2) cytokines between the groups.

Conclusions

Characterization of the tumor microenvironment of CRLM revealed that although a limited number of activated T-cells infiltrate the tumor and initiate an immune response, the number of LIGHT + T cells infiltrating the tumor were very low. Techniques to decrease suppressive influences or augment the cytotoxic T-cell response are needed and may be possible through mechanisms that can increase intratumoral TIL LIGHT expression.

An obese 55-year-old woman with nonalcoholic fatty liver disease presented 7 years after resection of a T3N1 ileal carcinoid tumor with an elevated chromogranin A, multifocal metastatic disease to the liver, and carcinoid syndrome. She underwent right hepatic artery yttrium-90 (Y90) radioembolization, followed a month later by selective Y90 treatment to segment IV. She then presented to our clinic 10 months later, remaining symptomatic with flushing, diarrhea, anxiety, myalgia, pain, and persistent night sweats despite Sandostatin administration. At least 11 tumors were identified in the right lobe of the liver and three in segment IV on liver-specific imaging. These lesions were stable over a year with no new lesions. At exploration, there was marked hypertrophy of the left lateral segment due to the yttrium-90 treatment of segments IV-VIII, corresponding with preoperative volumetrics predicting a functional liver remnant (FLR) of 40% after extended right hepatectomy. The right lobe and segment IV were fibrotic, hard, and visibly damaged. The gland had a thick, fibrotic capsule, and the parenchyma was dense, inflexible, and difficult to dissect, consistent with the previously reported morbidity of these operations. Extended right hepatectomy was performed. Final pathology demonstrated 15 foci of metastatic well-differentiated neuroendocrine carcinoma that were negative for necrosis, as was expected given her continued symptoms despite radioembolization. Numerous amorphous spheres, frequently in clusters, were present in segments IV-VIII in vessels and approximating tumors consistent with prior Y90 radioembolization. The patient had an uneventful post-operative recovery and remains symptom free on follow-up. Treatment options for metastatic tumors to the liver have increased in recent years and currently include radioembolization in selected patients. Surgical cytoreduction and complete metastasectomy continue to offer improvement in symptoms, quality of life, and survival in patients with neuroendocrine liver metastases; however, hepatectomy after radioembolization is unique and carries increased morbidity/mortality, likely due to Y90-induced liver fibrosis. We demonstrate images of fibrotic yttrium-90 radiation-affected liver and histological sections of radioembolic microbeads in blood vessels and distributed around resected tumors.

Background

Adjuvant immunotherapy has improved outcomes in patients with advanced melanoma; however, the potential benefit for patients with pancreatic ductal adenocarcinoma (PDAC) remains unknown. The aim of this study was to determine the impact of adjuvant chemotherapy and immunotherapy (CTx-IT) compared with CTx alone on patient survival after resection of PDAC.

Study design

Patients who underwent resection of PDAC from 2004 to 2015 were identified from the National Cancer Database. Univariate and multivariate Cox proportional hazards models were used to determine predictors of overall survival (OS) based on the type of adjuvant therapy received. Patients who received adjuvant immunotherapy were compared with those who received adjuvant CTx alone by propensity score matching.

Results

Of 21,313 patients who received curative-intent resection for PDAC followed by adjuvant systemic therapy, 269 (1.3%) patients were treated with adjuvant CTx-IT. Propensity score matching resulted in a cohort of 477 patients: (229 CTx only and 248 CTx-IT). The 5-year OS was higher in the CTx-IT group compared with CTx alone (29.2% vs 18.3%; p = 0.0045). On multivariate analysis, the addition of adjuvant immunotherapy was associated was improved overall survival (hazard ratio 0.74; p = 0.007).

Conclusions

The addition of adjuvant immunotherapy to chemotherapy is associated with improved survival compared with chemotherapy alone after curative-intent resection of pancreatic adenocarcinoma. Future research is warranted to match specific immunotherapy agents with susceptible patient populations to improve outcomes for this aggressive disease.