Transcriptomic characterization of the histopathological growth patterns in breast cancer liver metastases.

Metastatic breast cancer (mBC) remains incurable and liver metastases (LM) are observed in approximately 50% of all patients with mBC. In some cases, surgical resection of breast cancer liver metastases (BCLM) is associated with prolonged survival. However, there are currently no validated marker to identify these patients. The interactions between the metastatic cancer cells and the liver microenvironment result in two main histopathological growth patterns (HGP): replacement (r-HGP), characterized by a direct contact between the cancer cells and the hepatocytes, and desmoplastic (d-HGP), in which a fibrous rim surrounds the tumor cells. In patients who underwent resection of BCLM, the r-HGP is associated with a worse postoperative prognosis than the d-HGP. Here, we aim at unraveling the biological differences between these HGP within ten patients presenting both HGP within the same metastasis. The transcriptomic analyses reveal overexpression of genes involved in cell cycle, DNA repair, vessel co-option and cell motility in r-HGP while angiogenesis, wound healing, and several immune processes were found overexpressed in d-HGP LM. Understanding the biology of the LM could open avenues to refine treatment of BC patients with LM.

Histopathological growth patterns and tumor-infiltrating lymphocytes in breast cancer liver metastases.

Liver is the third most common organ for breast cancer (BC) metastasis. Two main histopathological growth patterns (HGP) exist in liver metastases (LM): desmoplastic and replacement. Although a reduced immunotherapy efficacy is reported in patients with LM, tumor-infiltrating lymphocytes (TIL) have not yet been investigated in BCLM. Here, we evaluate the distribution of the HGP and TIL in BCLM, and their association with clinicopathological variables and survival. We collect samples from surgically resected BCLM (n = 133 patients, 568 H&E sections) and post-mortem derived BCLM (n = 23 patients, 97 H&E sections). HGP is assessed as the proportion of tumor liver interface and categorized as pure-replacement ('pure r-HGP') or any-desmoplastic ('any d-HGP'). We score the TIL according to LM-specific guidelines. Associations with progression-free (PFS) and overall survival (OS) are assessed using Cox regressions. We observe a higher prevalence of 'any d-HGP' (56%) in the surgical samples and a higher prevalence of 'pure r-HGP' (83%) in the post-mortem samples. In the surgical cohort, no evidence of the association between HGP and clinicopathological characteristics is observed except with the laterality of the primary tumor (p value = 0.049) and the systemic preoperative treatment before liver surgery (p value = .039). TIL is less prevalent in 'pure r-HGP' as compared to 'any d-HGP' (p value = 0.001). 'Pure r-HGP' predicts worse PFS (HR: 2.65; CI: (1.45-4.82); p value = 0.001) and OS (HR: 3.10; CI: (1.29-7.46); p value = 0.011) in the multivariable analyses. To conclude, we demonstrate that BCLM with a 'pure r-HGP' is associated with less TIL and with the worse outcome when compared with BCLM with 'any d-HGP'. These findings suggest that HGP could be considered to refine treatment approaches.

Histopathological growth pattern of liver metastases as an independent marker of metastatic behavior in different primary cancers.

Surgical resection can lead to prolonged survival in patients with isolated liver metastases (LM) from various primary cancers. However, there are currently no validated predictive markers to discriminate between these oligo/argometastatic patients, who will benefit from surgery, and those with diffuse metastatic behavior in whom surgery will be futile. To evaluate whether the tumor microenvironment, or histopathological growth pattern (HGP), of LM reflects the type of metastatic progression independently of the origin of the primary cancer, we analyzed a combined series of patients who underwent surgery for colorectal LM (N=263) or non-colorectal LM (N=66). HGPs of LM were scored in each patient to distinguish between desmoplastic HGP (all LM showing a complete encapsulated pattern) and non-desmoplastic HGP (at least one LM with some infiltrating-replacement component). In the entire series, 5-year overall and progression-free survival were, 44.5% and 15.5%, respectively, with no significant differences between colorectal and non-colorectal LM. In patients with desmoplastic HGP, 5-year overall and progression-free survival were 57% and 32%, respectively, as compared to 41% and 12%, respectively, in patients with non-desmoplastic-HGP (p=0.03 and 0.005). Irrespective of cancer origin and compared to traditional risk factors, desmoplastic HGP was the most significant predictor for better post-operative overall survival (adjusted HR: 0.62; 95% CI: [0.49-0.97]; p=0.035) and progression-free survival (adjusted HR: 0.61; 95% CI: [0.42-0.87], p=0.006). This suggests that the HGP of LM may represent an accurate marker that reflects the mode of metastatic behavior, independently of primary cancer type.

Prognostic value of peritoneal scar-like tissue in patients with peritoneal metastases of ovarian origin presenting for curative-intent cytoreductive surgery.

BACKGROUND: Complete cytoreductive surgery (CRS), remain the gold standard in the treatment of peritoneal metastases of ovarian cancer (PMOC). Given the increasing rate of neoadjuvant chemotherapy in patients with high PCI, prior abdominal surgeries, inflammation and fibrotic changes, the benefit of removing any "peritoneal scar-like tissues" (PST) during CRS, hasn't been thoroughly investigated. Our objective in this retrospective cohort was to identify the proportion of malignant cells positivity in PST of patients with PMOC, undergoing curative-intent CRS ± HIPEC. METHODS: This is a retrospective study, conducted at our comprehensive cancer center, including patients with PMOC, presenting for curative-intent CRS. During CRS, benign-looking peritoneal lesions, lacking the typical hard nodular, aggressive, and invasive morphology, were systematically resected or electro fulgurated. PSTs were analyzed for the presence of tumoral cells by our pathologist. Correlations between the presence of PST and their positivity, and the different patients' variables, were studied. RESULTS: In 51% of patients, PST harbored malignant cells. Those were associated with poorly differentiated serous tumors, a high PCI (> 8) and a worse DFS: 17 months in the positive PST group versus 29 months in the negative PST group (p = 0.05), on univariate analysis. Multivariate analysis revealed that PCI > 8 and poorly differentiated primary tumor histology were correlated with a worse DFS, and that higher PCI and advanced FIGO were correlated with a worse OS. CONCLUSION: Benign-looking PST harbors malignancy in 51% of cases. The benefit of their systematic resection and their prognostic value should be further investigated in larger cohorts.

Association between primary tumor characteristics and histopathological growth pattern of liver metastases in colorectal cancer.

INTRODUCTION: The microarchitecture of liver metastases (LMs), or histopathological growth pattern (HGP), has been demonstrated to be a significant prognostic factor in patients undergoing resection of colorectal liver metastases (CRLMs). Currently, however, HGP can be only determined on the operative specimen. Therefore, the development of new tools to predict the HGP of CRLMs before surgery and to understand the mechanisms that drive these patterns is important for improving individualization of therapeutic management. In this study, we analyzed data from a retrospective series of patients who underwent surgery for CRLMs to compare primary tumor characteristics, including markers of local aggressiveness and migratory capacity, and HGP of liver metastases. METHODS: Data from a retrospective series of 167 patients who underwent curative-intent resection of CRLMs and in whom pathological samples from both primary tumor and liver metastases were available were reviewed. At the primary tumor level, KRAS mutational status, grade of differentiation, and tumor budding were assessed. HGP was scored in each resected CRLM, according to consensus guidelines, and classified as desmoplastic (dHGP) or non-desmoplastic (non-dHGP). Associations between primary tumor characteristics and HGP of CRLMs were evaluated using a binary logistic regression model. Overall survival and disease-free survival were evaluated using Kaplan-Meier and multivariable Cox regression analyses. RESULTS: CRLMs were classified as dHGP in 36% of the patients and as non-dHGP in 64%. Higher rates of moderately or poorly differentiated primary tumors were observed in the non-dHGP CRLM group (80%), as compared with the dHGP group (60%) (OR = 3.6; 95%CI: 1.6-7.05; p = 0.001). Higher rates of tumor budding were observed in the non-dHGP CRLM group, with a median tumor budding value of 4 as compared with 2.5 in the dHGP group (p = 0.042). In the entire series, 5-year overall and disease-free survival were 43% and 32.5%, respectively. The non-dHGP CRLM group had worse post-hepatectomy survival, with 5-year overall and disease-free survival of 32.2% and 24.6%, respectively, as compared with 60.8% and 45.9%, respectively, for the dHGP group (p = 0.02). CONCLUSION: Colorectal tumors with moderate or poor differentiation and those with high tumor budding are more frequently associated with CRLMs with a non-dHGP. This suggests that primary tumor characteristics of local aggressiveness and migratory capacity could preferentially promote the development of CRLMs with an infiltrating pattern and that these parameters should be considered as part of new scores for predicting HGP before surgery. This finding may stimulate new lines of research for more individualized therapeutic decision in patients with CRLM candidate to surgery.

A giant parastomal hernia in a high risk patient: preparation to make surgery worthwhile.

BACKGROUND: Parastomal hernia (PH) is a frequent and well-known complication of stoma placement. Most PHs are asymptomatic and those who are not are usually well tolerated by patients. Thus, watchful waiting is a common practice. Nevertheless, this management policy is associated with a risk of complications and with an inevitable risk of hernia enlargement, complicating its subsequent surgery. Moreover, PH can affect body image and alter the quality of life. METHODS: We herein present a complex case of a 67-year-old man with multiple comorbidities, who presented with an uncommon, below knee, giant PH, which was managed in a two-steps surgery by a multidisciplinary team comprising a senior digestive surgeon, experienced in abdominal wall repair, cardiologist, pulmonologist, anesthesiologist, psychiatrist, dietitian and physiotherapist. RESULT: Treatment started with 8 months hygienic measures comprising smoking cessation, strict control of diabetes and hypertension, a strict diet, and a physical fitness and pulmonary rehabilitation program. Two steps surgery started by colostomy transposition along with pre-peritoneal mesh repair to the right side and the second step consisted of a prophylactic PH repair using a Key-hole preperitoneal polypropelene mesh. CONCLUSION: PH is a common and sometimes inevitable complication of stoma creation. The success achieved by operating a heavily morbid patient, is only possible through the combined efforts of the multidisciplinary team and a preoperative rigorous management.

Tumor biology reflected by histological growth pattern is more important than surgical margin for the prognosis of patients undergoing resection of colorectal liver metastases.

INTRODUCTION: The histological growth pattern (HGP) of colorectal liver metastases (CRLMs) reflects tumor biology and local infiltrating behavior. In patients undergoing surgery for CRLMs, we investigated whether HGP and surgical margin status interact when influencing prognosis. METHODS: Clinicopathological data, margin status, and HGP were reviewed in patients who underwent resection of CRLMs. R1 margin was defined when cancer cells were present at any point along the margin. HGPs were scored according to international guidelines, identifying patients with desmoplastic (DHGP) or non-desmoplastic (non-DHGP) CRLMs. RESULTS: Among 299 patients, 16% had R1 resection and 81% had non-DHGP CRLMs. Non-DHGP was the only predictive factor for R1 resection (18.7% versus 7.4% in DHGP, p = 0.04). Poorer 5-year overall survival was observed in both R1 and non-DHGP groups in univariate analysis (27.6% in R1 versus 45.6% in R0, p = 0.026, and 37.2% in non-DHGP versus 59.2% in DHGP, p = 0.013), whereas non-DHGP but not R1 remained associated with worse prognosis in multivariate analysis. In patients with non-DHGP, R1 margin has no prognostic impact. CONCLUSIONS: In patients undergoing resection of CRLMs, the prognostic value of poor tumor biology, such as in patients with non-DHGP, exceeds that of surgical radicality.

Prognostic Value of Preoperative Serological Biomarkers in Patients Undergoing Curative-Intent Cytoreductive Surgery for Colorectal Cancer Peritoneal Metastases.

BACKGROUND: Cytoreductive surgery (CRS) for peritoneal metastases of colorectal cancer (PMCRC) is associated with a high risk of postoperative morbidity, thus making patient selection of upmost importance. Further to data showing an association between preoperative serological biomarkers and patient outcome in various solid tumors, in this study we aim to evaluate their prognostic value in patients with PMCRC treated with curative intent. PATIENTS AND METHODS: This is a retrospective study including patients with PMCRC treated by complete CRS ± HIPEC at our institution between 2011 and 2020. Preoperative serological biomarkers, along with other standard clinicopathological variables, were studied to determine their prognostic value. RESULTS: A total of 94 out of 108 patients met the inclusion criteria. Forty-three patients (46%) presented with synchronous PM. The median peritoneal cancer index (PCI) was 6. On univariate analysis, a higher neutrophil-to-lymphocyte ratio (NLR) was associated with poor prognosis in terms of overall survival (OS) [cutoff 3.567, hazard ratio (HR) 2.8 (1.4-5.3), p = 0.002], whereas a higher platelet-to-lymphocyte ratio (PLR) predicted favorable prognosis in terms of disease-free survival (DFS) [cutoff 185.4, HR 1.9 (1.07-3.53), p = 0.030]. On multivariate analysis, NLR > 3.567, positive lymph nodes (LNs), and PCI > 7 were independent predictive factors for worse OS, whereas NLR > 3.567 and positive LNs were significantly associated with worse DFS. PLR > 185.4 was associated with better DFS. CONCLUSION: High preoperative NLR (> 3.567) and PLR (> 185.4) can predict outcome of patients with PMCRC treated by complete CRS ± HIPEC.

Histopathological growth patterns of liver metastasis: updated consensus guidelines for pattern scoring, perspectives and recent mechanistic insights.

The first consensus guidelines for scoring the histopathological growth patterns (HGPs) of liver metastases were established in 2017. Since then, numerous studies have applied these guidelines, have further substantiated the potential clinical value of the HGPs in patients with liver metastases from various tumour types and are starting to shed light on the biology of the distinct HGPs. In the present guidelines, we give an overview of these studies, discuss novel strategies for predicting the HGPs of liver metastases, such as deep-learning algorithms for whole-slide histopathology images and medical imaging, and highlight liver metastasis animal models that exhibit features of the different HGPs. Based on a pooled analysis of large cohorts of patients with liver-metastatic colorectal cancer, we propose a new cut-off to categorise patients according to the HGPs. An up-to-date standard method for HGP assessment within liver metastases is also presented with the aim of incorporating HGPs into the decision-making processes surrounding the treatment of patients with liver-metastatic cancer. Finally, we propose hypotheses on the cellular and molecular mechanisms that drive the biology of the different HGPs, opening some exciting preclinical and clinical research perspectives.

Histopathological growth patterns of resected non-colorectal, non-neuroendocrine liver metastases: a retrospective multicenter study.

BACKGROUND: Distinct Histopathological Growth Patterns can be identified in liver metastases from melanoma, breast and colorectal cancers. For each of these distinct liver metastasis types the HGP has proven a biomarker for survival after partial hepatectomy, with the desmoplastic type marking favourable prognosis. Whether HGPs can be considered a pan-cancer phenomenon remains unknown. This study therefore evaluates the presence of HGPs and their prognostic value across non-colorectal non-neuroendocrine liver metastases. METHODS: A retrospective multicentre cohort study was performed in patients who underwent curative intent resection of non-colorectal non-neuroendocrine liver metastasis. HGPs were assessed on Haematoxylin and Eosin slides according to consensus guidelines and classified as desmoplastic or non-desmoplastic. Overall- and recurrence-free survival were evaluated using Kaplan-Meier and multivariable Cox regression analysis. RESULTS: In total, 132 patients with liver metastasis from 25 different tumour types were eligible for analysis, of which 26 (20%) had a desmoplastic HGP. Five-year OS and RFS (95%CI) were 53% (36-78%) versus 40% (30-53%), and 33% (19-61%) versus 15% (9-27%) for patients with desmoplastic compared to non-desmoplastic metastases, respectively (p = 0.031 & p = 0.004). On multivariable analysis (adjusted HR [95%CI]) a desmoplastic HGP was prognostic for both OS (0.46 [0.25-0.86]) and RFS (0.38 [0.21-0.69]). CONCLUSIONS: This study demonstrates that HGPs apply to liver metastases across a wide variety of primary tumour origins. They hold a prognostic value in these cases, suggesting that HGPs could represent a pan-cancer biomarker for survival after surgical resection of liver metastases.

The effect of salivary bypass tube use on the prevention of pharyngo-cutaneous fistulas after total laryngectomy.

INTRODUCTION: The aim of this retrospective study was to assess the efficacy of Salivary Bypass Tube (SBT) for preventing pharyngo-cutaneous fistula (PCF) in a recent cohort of patients who underwent primary and salvage total laryngectomy (TL). METHODS: A consecutive series of 133 patients who underwent total laryngectomy between 1997 and 2019 was reviewed. The incidence of PCF was compared between patients who did not receive SBT (nSBT group; n = 55) and those preventively receiving SBT (SBT group; n = 78) in both primary and salvage TL. Risk factors for PCF were evaluated in a univariate and multivariate analyses. RESULTS: The overall PCF rate was 30%. Preoperative characteristics were similar between the nSBT and SBT groups, except for older age (p = 0.016), lower preoperative hemoglobin (p = 0.043), and lesser neoadjuvant chemotherapy (p = 0.015) in the SBT group. The rate of PCF the nSBT group, was 41.5%, compared to 21.8% in the SBT group (p = 0.020). In multivariate analysis, only the use of SBT was associated with lower risk of PCF (OR = 0.41 (95% CI 0.19-0.89), p = 0.026). This effect was verified only in the subgroup of patient operated for salvage TL (OR = 0.225; 95% CI 0.09-0.7; p = 0.008). CONCLUSION: The use of SBT in our series in salvage TL, appears to be associated with a decreased risk of PCF.

Clinico-metabolic characterization improves the prognostic value of histological growth patterns in patients undergoing surgery for colorectal liver metastases.

BACKGROUND AND OBJECTIVES: The histological growth pattern (HGP) represents a strong prognostic factor in patients undergoing surgery for colorectal liver metastases (CRLM). We evaluated whether the combination of HGP with clinico-metabolic parameters could improve its prognostic value. METHODS: In a series of 108 patients undergoing resection of CRLM, the HGP of CRLM was scored according to international guidelines. Baseline clinico-metabolic clinical status was evaluated using a metabolic-Clinical Risk Score (mCRS), combining traditional Memorial Sloan Kettering-CRS parameters with the tumor-to-liver glucose uptake ratio as measured with 18 Fluorodeoxyglucose/positron emission tomography. RESULTS: In patients with desmoplastic HGP (DHGP) CRLM (20% of all patients), 5- and 10-years overall survival (OS) and disease free survival (DFS) were 66% and 43% and 37% and 24.5%, as compared with 35% and 21% and 11% and 11% in the non-DHGP group (p = 0.07 and 0.054). Among DHGP patients, those with a low-risk mCRS had improved postoperative outcomes, 5- and 10-years OS and DFS reaching 83.3% and 62.5% and 50% and 33%, as compared with 18% and 0% and 0% and 0% in high-risk mCRS patients (p = 0.007 and 0.003). In contrast, mCRS did not influence postoperative survivals in non-DHGP patients. CONCLUSIONS: Combining the clinico-metabolic characteristics with the HGP may improve prognostication in patients undergoing surgery for CRLM.

The absence of benefit of perioperative chemotherapy in initially resectable peritoneal metastases of colorectal cancer origin treated with complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: A retrospective analysis.

INTRODUCTION: The aim of this study was to compare the outcome of patients with peritoneal metastasis (PM) of colorectal origin treated with complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) with or without perioperative systemic chemotherapy (PCT+/PCT-). PATIENTS AND METHODS: Retrospective analysis of 125 patients treated with complete CRS (R0/R1) and HIPEC for PM from colorectal origin in two Belgian academic centers between 2008 and 2017. Disease-free survival (DFS) and overall survival (OS) were assessed with regard to PCT. Statistical analyses were adjusted for non-balanced survival risk factors. RESULTS: The PCT+ group (n = 67) received at least 5 cycles of PCT and the PCT-group (n = 56) did not receive PCT. The groups were well balanced for all prognostic factors except presentation of synchronous disease (more in PCT+). Survival analysis was adjusted to peritoneal cancer index and presentation of synchronous disease. After a median follow-up of 54±5-months, the 1, 3, 5-years OS in the PCT+ group were 98%, 59% and 35% compared to 97%, 77% and 56% in the PCT-group (HR = 1.46; 95% CI:0.87-2.47; p = 0.155). The 1,3 and 5 years DFS in the PCT+ group were 47%, 13% and 6% compared to 58%, 29% and 26% respectively in the PCT- (HR = 1.22; 95% CI:0.78-1.92; p = 0.376). CONCLUSION: This study does not show any clear benefit of PCT in carefully selected patients undergoing R0/R1 CRS and HIPEC for colorectal PM. The ongoing CAIRO6 trial randomizing CRS/HIPEC versus CRS/HIPEC and PCT will probably clarify the role of PCT in patients with resectable PM.

Association between the histopathological growth patterns of liver metastases and survival after hepatic surgery in breast cancer patients.

Currently, there are no markers to identify patients with liver-only or liver-dominant metastases that would benefit from hepatic surgery. Here we characterized histopathological growth patterns (HGPs) of liver metastases in a consecutive series of 36 breast cancer patients who underwent hepatic surgery. Survival analyses showed that the presence of a desmoplastic HGP in the liver metastases (a rim of fibrous tissue separating cancer cells from the liver parenchyma, present in 20 (56%) patients) is independently associated with favorable progression-free and overall survival when compared with the replacement HGP (cancer cells growing into the liver parenchyma, present in 16 (44%) patients).

The lack of selection criteria for surgery in patients with non-colorectal non-neuroendocrine liver metastases.

BACKGROUND: The benefit of surgery in patients with non-colorectal non-neuroendocrine liver metastases (NCRNNELM) remains controversial. At the population level, several statistical prognostic factors and scores have been proposed but inconsistently verified. At the patient level, no selection criteria have been demonstrated to guide individual therapeutic decision making. We aimed to evaluate potential individual selection criteria to predict the benefit of surgery in patients undergoing treatment for NCRNNELM. METHODS: Data for 114 patients undergoing surgery for NCRNNELM were reviewed. In this population, we identified an early relapse group (ER), defined as patients with unresectable recurrence < 1 year postoperatively who did not benefit from surgery (N = 28), and a long-term survival group (LTS), defined as patients who were recurrence-free ≥ 5 years postoperatively and benefited from surgery (N = 20). Clinicopathologic parameters, the Association Française de Chirurgie (AFC) score, and a modified 4-point Clinical Risk Score (mCRS) (excluding CEA level) were analyzed and compared between LTS and ER groups. RESULTS: The majority of patients were female and a majority had an ASA score ≤ 2 at the time of liver surgery. The median age was 55 years. Almost half of the patients (46%) presented with a single-liver metastasis. Intermediate- and low-risk AFC scores represented 40% and 60% of the population, respectively. Five- and 10-year overall survival (OS) and disease-free survival (DFS) rates were 56% and 27%, and 30% and 12%, respectively. Negative prognostic factors were the size of liver metastases > 50 mm and delay between primary and NCRNNELM <24 months for OS and DFS, respectively. AFC score was not prognostic while high-risk mCRS (scores 3-4) was predictive for the poorer OS. The clinicopathologic parameters were similar in the ER and LTS groups, except the presence of N+ primary tumor, and the size of liver metastases was significantly higher in the ER group. CONCLUSION: In patients with resectable NCRNNELM, no predictive factors or scores were found to accurately preoperatively differentiate individual cases in whom surgery would be futile from those in whom surgery could be associated with a significant oncological benefit.

Retrospective analysis of the immunogenic effects of intra-arterial locoregional therapies in hepatocellular carcinoma: a rationale for combining selective internal radiation therapy (SIRT) and immunotherapy.

BACKGROUND: Immunotherapy represents a promising option for treatment of hepatocellular carcinoma (HCC) in cirrhotic patients but its efficacy is currently inconsistent and unpredictable. Locoregional therapies inducing immunogenic cell death, such as transarterial chemoembolization (TACE) or selective internal radiation therapy (SIRT), have the potential to act synergistically with immunotherapy. For the development of new approaches combining locoregional treatments with immunotherapy, a better understanding of the respective effects of TACE and SIRT on recruitment and activation of immune cells in HCC is needed. To address this question, we compared intra-tumor immune infiltrates in resected HCC after preoperative treatment with TACE or SIRT. METHODS: Data fromr patients undergoing partial hepatectomy for HCC, without preoperative treatment (SURG, n = 32), after preoperative TACE (TACE, n = 16), or preoperative SIRT (n = 12) were analyzed. Clinicopathological factors, tumor-infiltrating lymphocytes (TILs), CD4+ and CD8+ T cells, and granzyme B (GZB) expression in resected HCC, and postoperative overall and progression-free survival were compared between the three groups. RESULTS: Clinicopathological and surgical characteristics were similar in the three groups. A significant increase in TILs, CD4+ and CD8+ T cells, and GZB expression was observed in resected HCC in SIRT as compared to TACE and SURG groups. No difference in immune infiltrates was observed between TACE and SURG patients. Within the SIRT group, the dose of irradiation affected the type of immune infiltrate. A significantly higher ratio of CD3+ cells was observed in the peri-tumoral area in patients receiving < 100 Gy, whereas a higher ratio of intra-tumoral CD4+ cells was observed in patients receiving > 100 Gy. Postoperative outcomes were similar in all groups. Irrespective of the preoperative treatment, the type and extent of immune infiltrates did not influence postoperative survival. CONCLUSIONS: SIRT significantly promotes recruitment/activation of intra-tumor effector-type immune cells compared to TACE or no preoperative treatment. These results suggest that SIRT is a better candidate than TACE to be combined with immunotherapy for treatment of HCC. Evaluation of the optimal doses for SIRT for producing an immunogenic effect and the type of immunotherapy to be used require further evaluation in prospective studies.

The burden of low anterior resection syndrome on quality of life in patients with mid or low rectal cancer.

BACKGROUND: Low anterior resection (LAR) with total mesorectal excision (TME) for mid and low rectal cancer is standard of care, reducing local recurrence and enhancing long-term survival. However, this surgery is associated with a constellation of major defecatory problems that are collectively referred to as low anterior resection syndrome (LARS). The aims of this study were to evaluate the frequency of LARS in patients who have undergone LAR and to assess the impact of LARS on long-term quality of life (QoL). METHODS: This was a single-center prospective survey study on patients who underwent LAR and TME for low or mid rectal cancer between 2007 and 2015. LARS score and QLQ-C30 questionnaires were used to evaluate patient's bowel functions and quality of life, respectively. Associations between LARS and QoL were evaluated. RESULTS: Fifty-seven patients out of 65 eligible agreed to participate in the study. Forty-three (66%) patients returned complete questionnaires. Five patients (11.6%) had no LARS, 7 had minor LARS (16.3%), and 31 had major LARS (72.1%). In univariate analysis, BMI > 30 kg/m2 was predictive of major LARS (p = 0.047). Major LARS did not impair global QoL (p = 0.75), function scores, or social scales, and was not associated with any of the symptom scores except for diarrhea (p = 0.02). CONCLUSION: LARS is a frequent occurrence after LAR and TME for rectal cancer (72.1%) and is more prevalent in morbidly obese patients. However, the occurrence of LARS does not appear to have a direct impact on QoL except for the occurrence of diarrhea.

Extended time interval between diagnosis and surgery does not improve the outcome in patients operated for resection or ablation of breast cancer liver metastases.

BACKGROUND: Breast cancer liver metastases (BCLM) is considered a systemic disease with poorly defined selection criteria for surgery and little evidence for the appropriate timing of surgery. METHODS: Postoperative outcomes of patients operated for BCLM were retrospectively reviewed and compared based on the timing of surgery, with the early surgery (ES) group treated ≤12 months after BCLM diagnosis, and late surgery (LS) group operated >12 months after diagnosis. RESULTS: Seventy-two patients with BCLM underwent liver surgery, including 37 and 35 in the ES and LS groups, respectively. Demographic and preoperative characteristics were similar between the groups, except that multifocal liver disease was more frequent in the LS group (p = 0.008). The LS group had a morbidity rate of 38%, compared to 11% in the ES group (p = 0.015). No postoperative deaths occurred. In the whole cohort, median progression-free (PFS) and overall survival (OS) were 19 and 50 months, respectively, and 1-, 3- and 5-year PFS and OS were 63%, 41%, 24% and 93%, 66%, 43%, respectively, with no significant difference observed between the ES and LS groups. Multivariate analysis revealed that breast cancer progesterone receptor negativity (HR = 3.34, p = 0.03) and a size of LM > 40 mm (HR = 3.11, p = 0.01) were significant negative prognostic factors for PFS. Only a size of LM > 40 mm (HR = 2.79, p = 0.008) was significantly associated with shorter OS. CONCLUSION: A prolonged preoperative observational period does not improve long-term outcomes after liver surgery in patients with resectable BCLM, suggesting that early management can safely be proposed to those patients, with good oncological outcomes.