Dual-energy computed tomography-based iodine concentration as a predictor of histopathological response to preoperative chemoradiotherapy for pancreatic cancer.

To explore predictors of the histopathological response to preoperative chemoradiotherapy (CRT) in patients with pancreatic cancer (PC) using dual-energy computed tomography-reconstructed images. This retrospective study divided 40 patients who had undergone preoperative CRT (50-60 Gy in 25 fractions) followed by surgical resection into two groups: the response group (Grades II, III and IV, evaluated from surgical specimens) and the nonresponse group (Grades Ia and Ib). The computed tomography number [in Hounsfield units (HUs)] and iodine concentration (IC) were measured at the locations of the aorta, PC and pancreatic parenchyma (PP) in the contrast-enhanced 4D dual-energy computed tomography images. Logistic regression analysis was performed to identify predictors of histopathological response. Univariate analysis did not reveal a significant relation between any parameter and patient characteristics or dosimetric parameters of the treatment plan. The HU and IC values in PP and the differences in HU and IC between the PP and PC (ΔHU and ΔIC, respectively) were significant predictors for distinguishing the response (n = 24) and nonresponse (n = 16) groups (P < 0.05). The IC in PP and ΔIC had a higher area under curve values [0.797 (95% confidence interval, 0.659-0.935) and 0.789 (0.650-0.928), respectively] than HU in PP and ΔHU [0.734 (0.580-0.889) and 0.721 (0.562-0.881), respectively]. The IC value could potentially be used for predicting the histopathological response in patients who have undergone preoperative CRT.

Response prediction in patients with gastric and esophagogastric adenocarcinoma under neoadjuvant chemotherapy using targeted gene expression analysis and next-generation sequencing in pre-therapeutic biopsies.

OBJECTIVES: Perioperative chemo-(radio-) therapy is the accepted standard in European patients with locally advanced adenocarcinoma of the esophagogastric junction or stomach (AEG/AS). However, 30-85% of patients do not respond to this treatment. The aim of our study was the identification of predictive biomarkers in pre-therapeutic endoscopic tumor biopsies from patients with histopathologic response (Becker-1) versus non-response (Becker-2/3) to preoperative chemotherapy. METHODS: Formalin-fixed paraffin-embedded biopsies from 36 Caucasian patients (Becker-1 n = 11, Becker-2 n = 7, Becker-3 n = 18) with AEG/AS, taken prior to neoadjuvant chemotherapy were selected. For RNA expression analysis, we employed the NanoString nCounter System. To identify genomic alterations like single nucleotide variants (SNV), copy number variation (CNV) and fusion events, we used Illumina TST170 gene panel. For HER2 and FGFR2 protein expression, immunostaining was performed. Furthermore, we analyzed the microsatellite instability (MSI) and Epstein-Barr virus (EBV) infection status by EBER in situ hybridization. RESULTS: Heat map and principal component analyses showed no clustering by means of gene expression according to regression grade. Concerning two recently proposed predictive markers, our data showed equal distribution for MSI (Becker-1: 2; Becker-2: 1; Becker-3: 3; out of 29 tested) and EBV infection was rare (1/32). We could not reveal discriminating target genes concerning SNV, but found a higher mutational burden in non-responders versus responders and fusion (in 6/14) and CNV events (in 5/14) exclusively in Becker-3. CONCLUSIONS: Although we could not identify discriminating target genes, our data suggest that molecular alterations are in general more prevalent in patients with AEG/AS belonging to the non-responding Becker group 3.

Immunotherapy for metastatic liver disease from colorectal carcinoma: case series from the Middle East.

Immunotherapy poses new considerations and alterations to the management of metastatic colorectal carcinoma (mCRC), where chemotherapy achieves complete radiological response but yields complete pathological response in few patients only. Immunotherapy may be superior in the conversion of unresectable disease to resectable liver lesions from mCRC and downsizing borderline lesions for more feasible resectability and achieving complete pathologic response, with the potential for cure and to alter current, established guidelines for surgical resection with a shift from chemotherapy. We present two patients with hepatic lesions from mCRC characterized by deficient mismatch repair (dMMR) which were unresectable after traditional chemotherapy but were converted to resectable lesions with a complete histopathological response following immunotherapy. Complete histopathologic response and radiologic regression or disappearance of liver lesions was observed in patients with dMMR mCRC after pembrolizumab. Immunotherapy exhibits notable potential for cure, achieving complete, successful surgical resection and improving prognosis.

Pathological Evaluation of Resected Colorectal Liver Metastases: mFOLFOX6 Plus Bevacizumab versus mFOLFOX6 Plus Cetuximab in the Phase II ATOM Trial.

We compared the preplanned histopathological responses of resected liver metastases from patients who received modified FOLFOX6 plus bevacizumab or modified FOLFOX6 plus cetuximab for liver-limited colorectal metastases in the ATOM trial. Fibrosis and viable tumor cells in tumor regression grade (TRG), infarct-like necrosis in modified TRG (mTRG), and dangerous halo (DH) were assessed. Fifty-five patients (28 and 27 patients in the bevacizumab and cetuximab arms, respectively) were divided into the low (viable tumor cells ≤ 50%) and high (>50%) TRG or mTRG groups. DH was characterized as absent/rare or focal/diffuse. Compared to the bevacizumab arm, the cetuximab arm was more effective, with respect to low TRG (13 vs. 23 patients) and absent/rare DH (14 vs. 19 patients), respectively. Low mTRG was similarly observed in both arms. Low TRG/mTRG and absent/rare DH showed better relapse-free survival (RFS) than high TRG/mTRG and focal/diffuse DH. In the bevacizumab arm, a significant difference in RFS existed between the low and high TRG groups, while in the cetuximab arm, for TRG, mTRG, and DH, the low and absent/rare groups demonstrated significantly longer RFS than the high and focal/diffuse groups, respectively. TRG could estimate RFS in patients who underwent liver metastasectomy after bevacizumab or cetuximab chemotherapy.

Clinical Utility of Circulating Tumor Cells for Predicting Major Histopathological Response after Neoadjuvant Chemoradiotherapy in Patients with Esophageal Cancer.

BACKGROUND: A "surgery as needed" approach may be offered to patients with esophageal cancer (EC) who achieve major histopathological response (MaHR) after neoadjuvant chemoradiotherapy (nCRT). However, the utility of clinical response assessment (CRE) for predicting histopathological response to nCRT remains limited. Circulating tumor cells (CTCs) hold promise as biomarkers of response to nCRT. METHODS: We analyzed the clinical utility of post-nCRT CTCs, alone or in combination with CRE, in the prediction of MaHR. We defined MaHR as either the lack or a limited presence (≤10%) of vital residual tumor cells in the resected esophageal specimen in the absence of nodal involvement. RESULTS: Of the 48 study patients, 27 (56%) achieved MaHR. Patients with MaHR had a significantly lower CTCs count compared with those without (3.61 ± 4.53 versus 6.83 ± 5.22 per mL of blood, respectively; P = 0.027). Using a cutoff for positivity of 5 CTCs per mL of blood, the combination of CTCs and CRE allowed achieving a negative predictive value for MaHR of 93% (95% confidence interval [CI] = 70-99%) along with a false negative rate of 5% (95% CI = 1-33%). CONCLUSION: CTCs count assessed in combination with CRE can potentially help identify patients with EC who achieved MaHR after nCRT.

Response to neoadjuvant chemotherapy and survival in molecular subtypes of resectable gastric cancer: a post hoc analysis of the D1/D2 and CRITICS trials.

BACKGROUND: Epstein-Barr virus positivity (EBV+) and microsatellite instability (MSI-high) are positive prognostic factors for survival in resectable gastric cancer (GC). However, benefit of perioperative treatment in patients with MSI-high tumors remains topic of discussion. Here, we present the clinicopathological outcomes of patients with EBV+, MSI-high, and EBV-/MSS GCs who received either surgery only or perioperative treatment. METHODS: EBV and MSI status were determined on tumor samples collected from 447 patients treated with surgery only in the D1/D2 trial, and from 451 patients treated perioperatively in the CRITICS trial. Results were correlated to histopathological response, morphological tumor characteristics, and survival. RESULTS: In the D1/D2 trial, 5-year cancer-related survival was 65.2% in 47 patients with EBV+, 56.7% in 47 patients with MSI-high, and 47.6% in 353 patients with EBV-/MSS tumors. In the CRITICS trial, 5-year cancer-related survival was 69.8% in 25 patients with EBV+, 51.7% in 27 patients with MSI-high, and 38.6% in 402 patients with EBV-/MSS tumors. Interestingly, all three MSI-high tumors with moderate to complete histopathological response (3/27, 11.1%) had substantial mucinous differentiation. No EBV+ tumors had a mucinous phenotype. 115/402 (28.6%) of EBV-/MSS tumors had moderate to complete histopathological response, of which 23/115 (20.0%) had a mucinous phenotype. CONCLUSIONS: In resectable GC, MSI-high had favorable outcome compared to EBV-/MSS, both in patients treated with surgery only, and in those treated with perioperative chemo(radio)therapy. Substantial histopathological response was restricted to mucinous MSI-high tumors. The mucinous phenotype might be a relevant parameter in future clinical trials for MSI-high patients.

Metabolic positron emission tomography/CT response after induction chemotherapy and chemo(re)irradiation is associated with higher negative resection margin rate in patients with locally recurrent rectal cancer.

AIM: Positron emission tomography (PET)/CT can be used to monitor the metabolic changes that occur after intensified treatment with induction chemotherapy and chemo(re)irradiation for locally recurrent rectal cancer (LRRC). This study aimed to analyse the correlation between the PET/CT response and final histopathological outcomes. METHODS: All LRRC patients who underwent induction chemotherapy prior to surgery between January 2010 and July 2020 and were monitored with pretreatment and post-treatment PET/CT were included. Visual qualitative analysis was performed, and patients were scored as having achieved a complete metabolic response (CMR), partial metabolic response (PMR) or no response (NR). The histopathological response was assessed according to the Mandard tumour regression (TRG) score and categorized as major (TRG 1-2), partial (TRG 3) or poor (TRG 4-5). The PET/CT and TRG categories were compared, and possible confounders were analysed. RESULTS: A total of 106 patients were eligible for analysis; 24 (23%) had a CMR, 54 (51%) had a PMR and 28 (26%) had NR. PET/CT response was a significant predictor of the negative resection margin rate, achieving 96% for CMR, 69% for PMR and 50% for NR. The overall accuracy between PET score and pathological TRG was 45%, and the positive predictive value for CMR was 63%. A longer interval between post-treatment PET/CT and surgery negatively influenced the predictive value. CONCLUSION: Metabolic PET/CT response evaluation after neoadjuvant treatment proves to be a complementary diagnostic tool to standard MRI in assessing tumour response, and may play a role for treatment planning in LRRC patients.

The value of repeat kidney biopsy in lupus nephritis. A systematic review / La utilidad de la biopsia renal repetida en nefritis lúpica. Una revisión sistemática

ABSTRACT A renal biopsy is the 'gold standard' for diagnosis and classification of lupus nephritis (LN). The role of repeat renal biopsy in lupus nephritis (LN) to guide treatment or predict prognosis has been controversial. A systematic literature review was conducted based on retrospective and prospective studies. The studies were identified using English electronic scientific databases, including MEDLINE PUBMED, published between January 1990 and August 2020. The eligibility criteria were studies including adult LN patients with at least one follow-up renal biopsy with appropriate longitudinal information. Case reports, studies with incomplete information or including duplicate patients were excluded. Based on the inclusion and exclusion criteria, a total of 73 publications were identified. This study included a total of 1167 repeat biopsies in LN patients from 15 studies. The primary indication for a repeat biopsy was relapse in 44-78% of the cases, and lack of response in 13-51%. Additionally, several repeat biopsies were done according to the protocol, after induction and maintenance therapy. In terms of histopathological class switches, there was a higher frequency of changes from nonproliferative to proliferative lesions. Only two studies provide a definition of histological response. There were often changes in the therapeutic approach after a repeat biopsy. Repeat kidney biopsies are helpful in patients with LN flare/relapse, and in patients with poor treatment response. Histological transformation was a common finding. The histologic and clinical responses are discordant. A repeat biopsy could be of prognostic value for therapeutic decision-making.

RESUMEN La biopsia renal es el «estándar de oro¼ para el diagnóstico y la clasificación de la nefritis lúpica (NL). El papel de la biopsia renal repetida en nefritis lúpica para orientar el tratamiento o predecir el pronóstico ha sido controversial. Se llevó a cabo una revisión sistemática de la literatura basada en estudios retrospectivos y prospectivos. Los estudios se identificaron a través de bases de datos científicas electrónicas en inglés, incluyendo Medline PubMed, de publicaciones entre enero de 1990 y agosto del 2020. Los criterios de elegibilidad fueron estudios que incluyeran a pacientes adultos con NL, quienes tuvieran al menos una biopsia renal de seguimiento, con información longitudinal apropiada. Se excluyeron informes de casos, estudios con información incompleta o con pacientes duplicados. Basándose en los criterios de inclusión y exclusión, se identificaron 73 publicaciones. En la presente revisión se analizaron un total de 1.167 biopsias repetidas en pacientes con NL en 15 estudios. Las principales indicaciones para la biopsia repetida fueron: recidiva en 44-78% de los casos, y falta de respuesta en 13-51%. Adicionalmente, varias biopsias repetidas se hicieron conforme al protocolo, luego de la terapia de inducción y de mantenimiento. Con respecto a los cambios de clase histopatológica, hubo una mayor frecuencia de cambios de lesiones no proliferativas a lesiones proliferativas. Solamente dos estudios ofrecen una definición de respuesta histológica. Con frecuencia hubo cambios en el abordaje terapéutico después de realizar la biopsia repetida. Las biopsias renales repetidas son útiles en pacientes con exacerbación/recidiva y en pacientes con falta de respuesta a tratamiento. La transformación histológica fue un hallazgo frecuente; las respuestas histológicas y clínicas son discordantes. Una biopsia repetida puede ser de valor pronóstico para la toma de decisiones terapéuticas.

Neoadjuvant chemotherapy-induced severe neutropenia is associated with histopathological response and survival in locally advanced gastric cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) has been shown to improve the prognosis for patients with locally advanced gastric cancer (LAGC). Neutropenia, a predominant chemotherapy-related adverse event, affects the therapeutic course for NAC. METHODS: Data for 233 patients with LAGC treated with NAC and curative gastrectomy at our center were retrospectively analysed in terms of the relationship between neutropenia and clinicopathological features or outcomes. RESULTS: NAC-induced neutropenia, NAC-induced severe (grade 3/4) neutropenia (NISN), and a favorable histopathological response (HPR) were observed in 102 (43.8%), 35 (15.0%), and 103 (44.2%) patients, respectively. Together with tumor differentiation, clinical response, and lymphovascular invasion (LVI), and NISN independently predicted a favorable HPR [odds ratio (OR) =4.158, 95% confidence interval (CI): 1.762-9.812, P=0.001). Among patients treated with postoperative chemotherapy, NISN independently predicted poor compliance with postoperative chemotherapy (OR 0.364, 95% CI: 0.148-0.894, P=0.028) and thus poor overall survival (OS) and disease-free survival (DFS). Among patients treated with preoperative chemotherapy alone, NISN was associated with a tendency towards a better DFS (P=0.116) and independently predicted superior OS (hazard ratio =0.253, 95% CI: 0.077-0.830, P=0.023). CONCLUSIONS: In conclusion, our study revealed a link between NISN, HPR, treatment compliance, and survival. NISN is useful for guiding treatment strategies and predicting prognosis for LAGC patients.

Approaches and genetic determinants in predicting response to neoadjuvant chemotherapy in locally advanced gastric cancer.

Gastric cancer remains a major health burden worldwide. There is near-universal agreement that neoadjuvant chemotherapy (NAC) is a preferred management for locally advanced gastric cancer (LAGC). However, the optimal approach for an individual patient is still not clear and remains controversial, which could be at least partly explained by the lack of predictive tools. The ability to predict chemosensitivity from NAC in routine clinical practice is difficult and is an area of intense investigation, especially in the Precision-Medicine Era. Available consistent evidence suggests that a favorable tumor histopathological response to NAC may be a useful positive prognostic marker in gastric cancer. Hence, it is reasonable to speculate that making the histopathological response from NAC predictable will dramatically facility the NAC and improve patients' outcome. This review provides an overview on the current status of predictive biomarkers for histopathological response from NAC in LAGC, including clinicopathological variables, imaging and molecular testing. Furthermore, limitations and future perspectives are also discussed.

Prognosis of patients with esophageal squamous cell carcinoma who achieve major histopathological response after neoadjuvant chemoradiotherapy.

BACKGROUND: The purpose of this study was to investigate the prognosis and its predictors in patients with esophageal squamous cell carcinoma (ESCC) who achieve major histopathological response (MaHR) after neoadjuvant chemoradiotherapy (nCRT). METHODS: We examined a total of 187 ESCC patients who achieved MaHR following nCRT and survived the perioperative period. MaHR was defined as either absence or <10% vital residual tumor cells (VRTC) in the resected esophagus without nodal involvement. Univariate and multivariate analyses were used to identify factors significantly associated with overall survival (OS). RESULTS: At the time of analysis, 113 patients (60.4%) were dead (5-year OS = 48%; median survival time = 54.8 months). The amount of VRTC (1-10% versus 0% VRTC; hazard ratio [HR] = 1.9, P < 0.001) and the thoroughness of histopathological examination (standard [≤ 4 tumor blocks] versus thorough [> 4 tumor blocks], HR = 1.57; P = 0.013) were independent predictors of OS in multivariate analysis. A stepwise increase in OS was observed in the following groups: patients with 1-10% VRTC identified by the standard protocol, patients with 1-10% VRTC identified by the thorough protocol, patients with 0% VRTC identified by the standard protocol, and patients with 0% VRTC identified by the thorough protocol (5-year OS rates = 20%, 40%, 50%, and 62%, respectively, P < 0.001). CONCLUSIONS: In ESCC patients who achieve MaHR after nCRT, the presence of microscopical residual disease and the thoroughness of histopathological examination are associated with survival.

New utility of an old marker: serum low-density lipoprotein predicts histopathological response of neoadjuvant chemotherapy in locally advanced gastric cancer.

BACKGROUND: Although the correlation between metabolic abnormality and gastric cancer has been extensively investigated, the question of whether metabolic parameters might influence the efficacy of chemotherapy in locally advanced gastric cancer is still unanswered. In our present study, we investigated the relationship between serum fasting glucose, lipid levels, and histopathological response of neoadjuvant chemotherapy (NAC) in locally advanced gastric cancers. PATIENTS AND METHODS: A total of 128 patients were identified from a prospectively maintained database of patients with locally advanced gastric cancer who received NAC between July 2004 and December 2012. Histopathological response after NAC was analyzed according to Becker's tumor-regression grade. Univariate analyses and multivariable regression analyses were performed to determine the correlation between tumor size, differentiation, fasting glucose, lipid levels, and tumor histopathological response after NAC. RESULTS: Univariate analysis revealed that low-density lipoprotein level and total cholesterol, as well as tumor size and differentiation, correlated significantly with histopathological response. Low-density lipoprotein levels and tumor size were found to be independent predictors for histopathological response, according to multivariable regression analyses. CONCLUSION: In this observational, hypothesis-generating study, serum low-density lipoprotein measurement was found to be useful in predicting chemosensitivity to locally advanced gastric cancer patients undergoing NAC. Incorporation of serum low-density lipoprotein levels into individualized treatment protocols could be considered in clinical practice.

PLK-1 Expression is Associated with Histopathological Response to Neoadjuvant Therapy of Hepatic Metastasis of Colorectal Carcinoma.

Polo-like kinase 1 (PLK1) is a serine/threonine-protein kinase expressed during mitosis and overexpressed in multiple human cancers, including leukemia and also many solid tumors. PLK1 knockdown has been shown to block proliferation of leukemic cell lines and the clonogenic potential of tumor cells grown from patients with cancer. PLK1 inhibition is a promising strategy for the treatment of some tumors. We aim to analyze expression of PLK1 in metastatic colorectal carcinoma. Retrospective analysis of colorectal carcinomas with hepatic metastasis during follow-up receiving neoadjuvant chemotherapy (NAC), based on oxaliplatin. Immunohistochemistry for PLK-1 in paraffin-embedded tissue from the primary and also from the metastasis. 50 patients. 32% showed good histopathological response. 43% of the primaries were positive for PLK1, as opposed to 23.5% of the metastasis. Expression of PLK1 was significantly reduced in metastasis compared with the primaries (p = 0.05), what could be due to therapy or to a phenotypic change of the metastatic nodule. Analysis of the prognostic influence of PLK1 expression showed significant association between PLK1 expression in metastasis and lower overall survival (p = 0.000). We have also found a significant association between PLK1 expression and histopathological response (p = 0.02). All the tumors with high expression of PLK1 showed minor response (11/11). This study shows the association between survival and poor histopathological response to therapy and high expression of PLK1 in metastasis. Our results could open a new therapeutic approach through the inhibition of PLK1.

18F-FDG-PET/CT can identify histopathological non-responders to platinum-based neoadjuvant chemotherapy in advanced epithelial ovarian cancer.

OBJECTIVE: The aim of this study was to examine the relationship between the reduction of maximum standardized uptake values (SUVmax) in 18F-FDG-PET/CT to histopathological changes obtained with neoadjuvant chemotherapy (NACT) in advanced epithelial ovarian cancer (EOC). We wanted to evaluate whether 18F-FDG-PET/CT is useful for identifying patients who will not respond to NACT and would therefore benefit from second-line chemotherapy instead of interval debulking surgery (IDS). METHODS: Twenty-six primarily inoperable EOC patients treated with NACT were enrolled in this study. 18F-FDG-PET/CT imaging was performed before diagnostic laparoscopy and after three to four NACT cycles. The relationship between the decrease in omental SUVmax from before to after NACT with omental histopathological response was examined in samples taken from the corresponding anatomical sites during IDS. Patients were divided into three groups according to chemotherapy-induced histopathological changes. Serum CA125 and HE4 halftimes during NACT as well as Ki-67 antigen expression in IDS samples were determined. RESULTS: The median omental SUVmax change during NACT was -64% (range-16% to -84%), and it was associated with histopathological response (p=0.004, OR 0.9, CI 0.84-0.97). A SUVmax decrease of less than 57% identified histopathological non-responders. Progression-free survival (PFS) differed between the poor, moderate and good histopathological response groups (0.9 year vs. 1.2 years vs. 1.4 years, respectively, p=0.05). The SUVmax change was not associated with PFS. CONCLUSION: 18F-FDG-PET/CT was able to identify patients who would not respond to NACT. To obtain a histopathological response in EOC, a substantial metabolic response in 18F-FDG-PET/CT is necessary.

Morphological aspects of the hepatic response to neoadjuvant therapy.

INTRODUCTION: Therapy of metastatic colorectal carcinoma has greatly evolved in recent years. Surgery is still the best curative option and can improve survival in stage IV disease. Neoadjuvant chemotherapy (NAC) has emerged as a widely used therapeutic option before surgery. Pathologists have developed several systems to grade response, mainly adapting the grading systems used for the response in primary esophageal or rectal tumors. There are many reports confirming the prognostic utility of these grading systems. However, there have been fewer references to the potential significance of the pattern of histological response. The objective of the present study is to describe the histopathological lesions found in the tumor bed after NAC and their potential significance in terms of prognosis. MATERIAL AND METHODS: We reviewed the files of patients with colorectal carcinoma that developed hepatic metastasis during follow-up and received NAC before surgical resection of metastasis. We gathered demographic, analytical and morphological data of the cases, and also reviewed the hepatic resection samples to measure the pathological response to chemotherapy according to Blazer's criteria, and to define the predominant patterns of response (mucin pools, fibrosis or necrosis). We also determined the presence of satellitosis, measured the thickness of the tumor-normal interface (TNI) as proposed by Maru et al., and searched for vascular and bile duct invasion. All these pieces of information were collected in an Excel database and analyzed with SPSS 20.0 for Windows statistical package. The outcome measures were disease-free survival and overall survival in months since the first surgery to resect metastatic disease. RESULTS: Fifty patients fulfilled the inclusion criteria for the present study. All of them had received a chemotherapeutic regimen mainly based on platinum, associated or not with targeted drugs (18% received anti-EGFR drugs and 24% anti-VEGFR drugs). Of the primaries, 66% were of sigmoid-rectal origin, and 32% of the cases showed a major histopathological response to therapy (including 3 cases with a complete response). In 76% of the tumors, the predominant histological pattern was necrosis, followed by fibrosis (57.4%). Mucin pools were the predominant feature in 23.4% of the tumors. We found satellitosis (microscopic tumor nodules separated by more than 1mm from the principal tumor) in 53.2% of the cases. A prominent inflammatory reaction was found in 19% of the cases, and it was mainly composed of lymphocytes and hystiocytes (70% of the cases). Vessel invasion was seen in 30% of the cases, and perineural invasion was only found in 4%. We found no case of bile duct invasion by the tumor. The thickness of the TNI measured less than 2.5mm in 60% of the present series. Statistical analysis of the series revealed that thickness of the tumor-liver interface was significantly associated with recurrence and overall survival. We found a significant association between response and thickness of the tumor-normal liver interface. In our series, the presence of satellitosis tended to predict a shorter DFS. The comparison of Kaplan-Meier curves with the log-rank test showed a significant association between overall survival and the presence of mucin pools and fibrosis in the tumor bed. The other histopathological factors did not predict differences in prognosis. These differences were independent of the use of targeted drugs. DISCUSSION: The pathological reports of hepatic metastasis from colorectal carcinoma resected after NAC usually indicate only the number, the size and the response of the tumor cells to therapy, apart from the distance to the resection margin of the specimen. Few reports have analyzed the possible prognostic significance of the different kinds of histopathological responses. The results of the present study indicate that those tumors with extensive pools of mucin show a significantly worse prognosis as compared to tumors with less mucin secretion. Fibrosis indicates a better prognosis, except when desmoplasia is present. Our study further supports the prognostic significance of the thickness of the tumor-hepatic interface. We conclude that pathology reports should specify the kind of histopathological response to therapy, besides grading it, because this might add significant prognostic information.