Perioperative FLOT plus ramucirumab for resectable esophagogastric adenocarcinoma: A randomized phase II/III trial of the German AIO and Italian GOIM.

This multicenter, randomized phase II/III study evaluated the addition of the vascular endothelial growth factor receptor-2 inhibitor ramucirumab to FLOT as perioperative treatment for resectable esophagogastric adenocarcinoma. Patients received either FLOT alone (Arm A) or combined with ramucirumab followed by ramucirumab monotherapy (Arm B). The primary endpoint for the phase II portion was the pathological complete or subtotal response (pCR/pSR) rate. Baseline characteristics were comparable between both arms with a high rate of tumors signet-ring cell component (A:47% B:43%). No between-arm difference in pCR/pSR rate was seen (A:29% B:26%), therefore the transition to phase III was not pursued. Nevertheless, the combination was associated with a significantly increased R0-resection rate compared with FLOT alone (A:82% B:96%; P = .009). In addition, the median disease-free survival was numerically improved in Arm B (A:21 months B:32 months, HR 0.75, P = 0.218), while the median overall survival was similar in both treatment arms (A:45 months B:46 months, HR 0.94, P = 0.803). Patients with Siewert type I tumors receiving transthoracic esophagectomy with intrathoracic anastomosis showed an increased risk of serious postoperative complications after ramucirumab treatment, therefore recruitment of those patients was stopped after the first-third of the study. Overall, surgical morbidity and mortality was comparable, whereas more non-surgical grade ≥ 3 adverse events were observed with the combination, especially anorexia (A:1% B:11%), hypertension (A:4% B:13%) and infections (A:19% B:33%). The combination of ramucirumab and FLOT as perioperative treatment shows efficacy signals, particularly in terms of R0 resection rates, for a study population with a high proportion of prognostically poor histological subtypes, and further evaluation in this subgroup seems warranted.

Systemic-inflammation-based score can predict prognosis in metastatic gastric cancer patients before first-line chemotherapy.

AIM: Systemic inflammatory response affects survival of gastric cancer (GC) patients. This study was carried out to create a prognostic inflammatory-based score to predict survival in metastatic GC (mGC) before first-line chemotherapy. MATERIALS & METHODS: We studied the prognostic value of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio in 151 patients with mGC at the diagnosis. RESULTS: Median overall survival (OS) was significantly lower in patients with high NLR. Performance status 1-2 according to the Eastern Cooperative Oncology Group scale and NLR were predictors of shorter OS at multivariate analysis. Based on these results, we defined a prognostic OS score, showing a better median OS in favorable risk group. CONCLUSION: Elevated pretreatment NLR and Eastern Cooperative Oncology Group are independent predictors of shorter OS in mGC patients before first-line chemotherapy.

Fluorescence-Guided Surgery in the Combined Treatment of Peritoneal Carcinomatosis from Colorectal Cancer: Preliminary Results and Considerations.

BACKGROUND: Indocyanine green (ICG) is a near-infrared fluorescent contrast agent, which preferentially accumulates in cancer tissue. The aim of our study was to investigate the role of fluorescence imaging (FI) with ICG (ICG-FI) for detecting peritoneal carcinomatosis (PC) from colorectal cancer (CRC). METHODS: Four CRC patients with PC scheduled for cytoreductive surgery + hyperthermic intraperitoneal chemotherapy were enrolled in this prospective study. At a median time of 50 min after 0.25 mg/kg ICG injected intravenously, intraoperative ICG-FI using Fluobeam® was performed in vivo and ex vivo on all specimens. The Peritoneal Cancer Index was used to estimate the likelihood of complete cytoreduction. RESULTS: No severe complications were recorded. ICG-FI took a median of 20 min (range 10-30, IQR 15-25). Sixty-nine nodules were harvested. Fifty-two nodules had been diagnosed preoperatively by conventional imaging (n = 30; 43%) or intraoperatively by visual inspection/palpation (n = 22; 32%). With ICG-FI, 47 (90%) nodules were hyperfluorescent, and five hypofluorescent. Intraoperative ICG-FI identified 17 additional hyperfluorescent nodules. On histopathology, 16 were metastatic nodules. Sensitivity increased from 76.9%, with the conventional diagnostic procedures, to 96.9% with ICG-FI. The positive predictive value of ICG-FI was 98.4%, and test accuracy was 95.6%. Diagnostic performance of ICG-FI was significantly better than preoperative (p = 0.027) and intraoperative conventional procedures (p = 0.042). The median PCI score increased from 7 to 10 after ICG-FI (p < 0.001). CONCLUSIONS: Our results suggest that intraoperative ICG-FI can improve outcomes in patients undergoing CS for PC from CRC. Further studies are needed to determine the role of ICG-FI in this patient population.

Indocyanine Green Fluorescence Imaging-Guided Surgery in Primary and Metastatic Liver Tumors.

BACKGROUND: After surgery for liver tumors, recurrence rates remain high because of residual positive margins or undiagnosed lesions. It has been suggested that detection of hepatic tumors can be obtained with near-infrared fluorescence imaging (FI). Indocyanine green (ICG) has been used with contrasting results. The aims of this study were to explore ICG-FI-guided surgery methodology and to assess its potential applications. MATERIALS AND METHODS: Out of 14 patients with liver tumors, 5 were not operated on, and 9 patients (3 primary and 6 metastatic tumors) underwent surgery. ICG (0.5 mg/kg) was injected intravenously 24 hours before surgery. Fluorescence was investigated prior to resection to detect liver lesions, during hepatic transection to guide surgery, on both cross-section and benchtop to assess surgical margins, and for pathological evaluation. RESULTS: All operations were successful and had a short duration. ICG-FI detected all already known lesions (n = 10), and identified 2 additional small tumors (1 hepatocarcinoma and 1 metastasis, diagnostic improvement = 20%). Two hepatocarcinomas were hyperfluorescent; the remaining one, with a central hypofluorescent area and a hyperfluorescent ring, was indeed a mixed cholangiohepatocarcinoma. All metastatic nodules were hypofluorescent with a hyperfluorescent rim. In all cases, in vivo and ex vivo fluorescence revealed clear liver margins. Postoperative pathological examination greatly benefited of liver fluorescence to assess radicality. CONCLUSION: ICG-FI-guided surgery was shown to be an effective tool to improve both intraoperative staging and radicality in the surgical treatment of primary and metastatic liver tumors.

What's New in Gastric Cancer: The Therapeutic Implications of Molecular Classifications and Future Perspectives.

Despite some remarkable innovations and the advent of novel molecular classifications the prognosis of patients with advanced gastric cancer (GC) remains overall poor and current clinical application of new advances is disappointing. During the last years only Trastuzumab and Ramucirumab have been approved and currently used as standard of care targeted therapies, but the systemic management of advanced disease did not radically change in contrast with the high number of molecular drivers identified. The Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG) classifications paved the way, also for GC, to that more contemporary therapeutic approach called "precision medicine" even if tumor heterogeneity and a complex genetic landscape still represent a strong barrier. The identification of specific cancer subgroups is also making possible a better selection of patients that are most likely to respond to immunotherapy. This review aims to critically overview the available molecular classifications summarizing the main druggable molecular drivers and their possible therapeutic implications also taking advantage of new technologies and acquisitions.

Naples Prognostic Score, Based on Nutritional and Inflammatory Status, is an Independent Predictor of Long-term Outcome in Patients Undergoing Surgery for Colorectal Cancer.

BACKGROUND: The existing scores reflecting the patient's nutritional and inflammatory status do not include all biomarkers and have been poorly studied in colorectal cancers. OBJECTIVE: The purpose of this study was to assess a new prognostic tool, the Naples prognostic score, comparing it with the prognostic nutritional index, controlling nutritional status score, and systemic inflammation score. DESIGN: This was an analysis of patients undergoing surgery for colorectal cancer. SETTINGS: The study was conducted at a university hospital. PATIENTS: A total of 562 patients who underwent surgery for colorectal cancer in July 2004 through June 2014 and 468 patients undergoing potentially curative surgery were included. MaxStat analysis dichotomized neutrophil:lymphocyte ratio, lymphocyte:monocyte ratio, prognostic nutritional index, and the controlling nutritional status score. The Naples prognostic scores were divided into 3 groups (group 0, 1, and 2). The receiver operating characteristic curve for censored survival data compared the prognostic performance of the scoring systems. MAIN OUTCOME MEASURES: Overall survival and complication rates in all patients, as well as recurrence and disease-free survival rates in radically resected patients, were measured. RESULTS: The Naples prognostic score correlated positively with the other scoring systems (p < 0.001) and worsened with advanced tumor stages (p < 0.001). Patients with the worst Naples prognostic score experienced more postoperative complications (all patients, p = 0.010; radically resected patients, p = 0.026). Compared with group 0, patients in groups 1 and 2 had worse overall (group 1, HR = 2.90; group 2, HR = 8.01; p < 0.001) and disease-free survival rates (group 1, HR = 2.57; group 2, HR = 6.95; p < 0.001). Only the Naples prognostic score was an independent significant predictor of overall (HR = 2.0; p = 0.03) and disease-free survival rates (HR = 2.6; p = 0.01). The receiver operating characteristic curve analysis showed that the Naples prognostic score had the best prognostic performance and discriminatory power for overall (p = 0.02) and disease-free survival (p = 0.04). LIMITATIONS: This is a single-center study, and its validity needs additional external validation. CONCLUSIONS: The Naples prognostic score is a simple tool strongly associated with long-term outcome in patients undergoing surgery for colorectal cancer. See Video Abstract at http://links.lww.com/DCR/A469.

NAB-paclitaxel and gemcitabine in metastatic pancreatic ductal adenocarcinoma (PDAC): from clinical trials to clinical practice.

BACKGROUND: Pancreatic adenocarcinoma is an aggressive disease with poor prognosis. In a randomized phase III trial, combination of Nab-paclitaxel (Nab-P) plus gemcitabine showed superior activity and efficacy in first-line treatment compared with gemcitabine alone. METHODS: Nab-P is not dispensed in Italy; however, we obtained this drug from our Ethics Committee for compassionate use. The aim of this study was to evaluate the efficacy and safety profile of this Nab-P and gemcitabine combination in a cohort of patients treated outside clinical trials. From January 2012 to May 2014, we included 41 patients with advanced pancreatic adenocarcinoma receiving combination of 125 mg/m(2) Nab-P and 1 g/m(2) gemcitabine on days 1, 8 and 15 of a 28-day cycle, as first-line treatment. Median age of patients was 67 (range 41-77) years, and 11 patients were aged ≥70 years. RESULTS: Eastern Co-operative Oncology Group performance status was 0 or 1 in 32 patients (78 %) and 2 in nine patients (22 %). Primary tumor was located in the pancreatic head or body/tail in 24 (58.5 %) and 17 (41.5 %) patients, respectively, and nine patients had received biliary stent implantation before starting chemotherapy. Median carbohydrate antigen 19-9 level was 469 U/l (range 17.4-61546 U/l) and 29 patients (70.7 %) had referred pain at the time of diagnosis. Patients received a median six cycles (range 1-14) of treatment. Overall response rate was 36.6 %; median progression-free survival was 6.7 months [(95 % confidence interval (CI) 5.966-8.034), and median overall survival was 10 months (95 % CI 7.864-12.136). Treatment was well tolerated. No grade 4 toxicity was reported. Grade 3 toxicity included neutropenia in 10 patients (24.3 %), thrombocytopenia in five (12 %), anemia in three (7.3 %), diarrhea in four (9.7 %), nausea and vomiting in two (4.9 %), and fatigue in six (14.6 %). Finally, pain control was achieved in 24 of 29 patients (82.3 %) with a performance status improvement of 10 % according to the Karnofsky scale. CONCLUSIONS: Our results confirm that combination of gemcitabine plus Nab-P is effective both in terms of overall response rate, progression-free survival and overall survival, with a good safety profile.

Is complete mesocolic excision with central vascular ligation safe and effective in the surgical treatment of right-sided colon cancers? A prospective study.

PURPOSE: Complete mesocolic excision (CME) with central vascular ligation (CVL) has been proposed for treatment of colon cancers based on the same principles as total mesorectal excision. Impressive outcomes have been reported, however, direct comparisons with the classic procedure are lacking. METHODS: Forty-five consecutive patients operated on in the last 5 years with CME and CVL right hemicolectomy entered the study. Fifty-eight right-sided colon cancer patients operated in the previous 5 years with classic approach constituted the control group. Intra- and postoperative course assessed the safety of the procedure. Primary end-points for oncological adequacy were recurrence and survival rate. RESULTS: All operations were successful with no increase in postoperative complications (p = 0.85). Number of harvested nodes and length of vascular ligation were shown to be significantly better in the CME group (p < 0.01). A higher number of tumor deposits were harvested thus allowing chemotherapy in newly upstaged patients. Locoregional recurrences were never experienced in CME patients (p = 0.03). The risk of cancer-related death was reduced by over one half in all CME patients, and even by three quarters in node-positive tumors. The classic operation was significantly associated with poor outcome (p < 0.01). CONCLUSION: This study shows that CME with CVL is a safe and effective surgical approach for right colon cancer, thus confirming the previously reported oncological adequacy. The procedure was shown to significantly decrease local recurrences and to improve the survival rate, particularly in node-positive patients. Urgent diffusion of this technique is warranted.

Presence of tumor deposits is a strong indicator of poor outcome in patients with stage III colorectal cancers undergoing radical surgery.

BACKGROUND: Tumor deposits (TDs) are emerging as an adverse prognostic factor in colorectal cancers (CRCs). However, TDs are somewhat neglected in the current staging system. It has been proposed either to add the TD count to the number of metastatic lymph nodes or to consider TDs as distant metastases; however, the scientific basis for these proposals seems questionable. This study aimed to investigate a new staging system. METHODS: A total of 243 consecutive patients with stage III CRC who were undergoing curative resection and adjuvant chemotherapy were included. Each substage of stage III TNM was split according to the absence or presence of TDs. Receiver operating characteristic (ROC) curves and bootstrap methods were used to compare the current vs the new competing staging system in terms of oncologic outcome prediction. RESULTS: A high rate of TDs was recorded (124 cases [51%]). TDs were correlated with other adverse prognostic indicators, particularly vascular and perineural invasions, and showed a negative correlation with the number of removed lymph nodes, suggesting a possible multimodal origin. In addition, TDs were confirmed to have a negative impact on oncologic outcome, regardless of their counts. Compared with the current staging system, the new classification displayed higher values at survival ROC analysis, a significantly better stratification of patients, and effective identification of patients at high risk of recurrence. CONCLUSIONS: TDs negatively affect the prognosis in CRCs. A revision of the staging system could be useful to optimize treatments. The proposed new classification is easy to implement and more accurate than the current one. This study was registered online on the ClinicalTrials.gov website under the following identifier: NCT05923450.

CD66c is a novel marker for colorectal cancer stem cell isolation, and its silencing halts tumor growth in vivo.

BACKGROUND: Despite the well recognized expression of the cell surface markers cluster of differentiation 44 (homing cell adhesion molecule) and CD133 (Prominin 1) on human colorectal cancer stem cells (CCSCs), these molecules do not appear to be effective targets for stem cell-directed therapies. Because the surface marker CD66c (also known as carcinoembryonic antigen-related cell adhesion molecule 6) has demonstrated promise as a therapeutic target in pancreatic malignancy, the authors evaluated its potential as a target for stem cell-directed treatment of colorectal cancer. METHODS: First, the authors characterized CD66c expression by flow cytometry and immunohistochemistry in colon cancer samples and in normal colon tissues. Then, the coexpression of CD66c and CD133 was evaluated on putative CCSCs. CD66c expression also was measured in stem cell-enriched colon spheres. Finally, the effects of small-interfering RNA-mediated CD66c silencing on the in vitro and in vivo growth of Caco2 colon cancer cells were evaluated. RESULTS: CD66c expression was significantly higher in colon cancers than in contiguous normal colon tissues and paralleled cancer stage. CD66c was absent in CD133-positive cells that were isolated from normal colon, whereas its expression was brightest (CD66c(bright) ) in CD133-positive cells from colon cancer samples. In vitro experiments demonstrated that colon spheres were considerably enriched in a CD66c(bright) population in a fashion comparable to the enrichment observed in fresh liver metastases. In vitro proliferation and clonogenic potential were hampered when CD66c was silenced in Caco2 cells. Finally, in vivo xenograft experiments demonstrated that CD66c silencing almost completely abrogated the tumorigenic potential of Caco2 cells. CONCLUSIONS: CD66c(bright) expression was associated with colon cancer stem cells and CD66c silencing blocked tumor growth, thereby opening the way to a potential new treatment for colon cancer.

Mallory-Weiss syndrome from giant gastric trichobezoar: A case report.

BACKGROUND: Mallory-Weiss syndrome (MWS), representing a linear mucosal laceration at the gastroesophageal junction, is a quite frequent cause of upper gastrointestinal bleeding, usually induced by habitual vomiting. The subsequent cardiac ulceration in this condition is likely due to the concomitance of increased intragastric pressure and inappropriate closure of the gastroesophageal sphincter, collectively inducing ischemic mucosal damage. Usually, MWS is associated with all vomiting conditions, but it has also been described as a complication of prolonged endoscopic procedures or ingested foreign bodies. CASE SUMMARY: We described herein a case of upper gastrointestinal bleeding in a 16-year-old girl with MWS and chronic psychiatric distress, the latter of which deteriorated following her parents' divorce. The patient, who was residing on a small island during the coronavirus disease 2019 pandemic lockdown period, presented with a 2-mo history of habitual vomiting, hematemesis, and a slight depressive mood. Ultimately, a huge intragastric obstructive trichobezoar was detected and discovered to be due to a hidden habit of continuously eating her own hair; this habit had persisted for the past 5 years until a drastic reduction in food intake and corresponding weight loss occurred. The relative isolation in her living status without school attendance had worsened her compulsory habit. The hair agglomeration had reached such enormous dimensions and its firmness was so hard that its potential for endoscopic treatment was judged to be impossible. The patient underwent surgical intervention instead, which culminated in complete removal of the mass. CONCLUSION: According to our knowledge, this is the first-ever described case of MWS due to an excessively large trichobezoar.

Assessment of the DNA Mismatch Repair System Is Crucial in Colorectal Cancers Necessitating Adjuvant Treatment: A Propensity Score-Matched and Win Ratio Analysis.

A deficient DNA mismatch repair (MMR) system is identified in a non-negligible part of sporadic colorectal cancers (CRCs), and its prognostic value remains controversial. High tumor mutational burden, along with a poor response to conventional chemotherapy and excellent results from immunotherapy, are the main features of this subset. The aim of this study was to evaluate the predictive value of DNA MMR system status for its best treatment. Four hundred and three CRC patients, operated on from 2014 to 2021 and not treated with immunotherapy, entered this study. Immunohistochemistry and polymerase chain reaction, as appropriate, were used to unequivocally group specimens into microsatellite stable (MSS) and instable (MSI) tumors. The win-ratio approach was utilized to compare composite outcomes. MSI tumors accounted for 12.9% of all series. The right tumor location represented the most important factor related to MSI. The status of the DNA MMR system did not appear to correlate with outcome in early-stage CRCs not requiring adjuvant treatment; in advanced stages undergoing conventional chemotherapy, MSI tumors showed significantly poorer overall and disease-free survival rates and the highest win ratio instead. The determination of DNA MMR status is crucial to recommending correct management. There is clear evidence that instable CRCs needing adjuvant therapy should undergo appropriate treatments.

Radiofrequency-assisted liver resection with a comb-shaped bipolar device versus clamp crushing: a clinical study.

BACKGROUND: In liver surgery, clamp-crushing (CC) procedure has been shown to be the most efficient system for liver transection. Recently, it has been suggested that radiofrequency-assisted liver resection (RFALR) may be more advantageous, but sufficient evidence has yet to be accumulated. METHOD: The control group was constituted by 32 patients undergoing CC liver transection. The study group included 13 patients undergoing RFALR with a new fully automated radiofrequency generator supplying a comb-shaped bipolar multielectrode device. RESULTS: RFALR allowed a faster hepatic transection and reduced both surgical time and intraoperative blood loss. RFALR was the only independent prognostic indicator of bleeding during liver transection. No significant liver damage and postoperative complications, particularly biliary leakage and stenosis, were experienced in the RFALR group. CONCLUSION: Compared with the CC procedure, this bipolar device was shown to be safe and effective in liver resections, allowing a very clean surgical field without increase of postoperative complications.

Giant retroperitoneal liposarcoma treated with radical conservative surgery: A case report and review of literature.

BACKGROUND: Retroperitoneal liposarcoma (RLPS) is a rare malignant tumor of the connective tissue and usually grows to a large size, undetected. Diagnosis is currently based on collective findings from clinical examinations and computed tomography (CT) and magnetic resonance imaging, the latter of which show a fat density mass and possible surrounding organ involvement. Surgical resection is the main therapeutic strategy. The efficacy and safety of further therapeutic choices, such as chemotherapy and radiotherapy, are still controversial. CASE SUMMARY: A 61-year-old man presented with complaint of a large left inguinal mass that had appeared suddenly, after a slight exertion. Ultrasonography revealed an omental inguinal hernia. During further clinical examination, an enormous palpable abdominal mass, continuing from the left inguinal location, was observed. CT revealed a giant RLPS, with remarkable mass effect and wide visceral dislocation. After multidisciplinary consultation, surgical intervention was performed. Subsequent neoadjuvant chemotherapy and radiotherapy were precluded by the mass' large size and retroperitoneal localization, features typically associated with non-response to these types of treatment. Instead, the patient underwent conservative treatment via radical surgical excision. After 1 year, his clinical condition remained good, with no radiological signs of recurrence. CONCLUSION: Conservative treatment via surgery resulted in a successful outcome for a large RLPS.

Prediction of SARS-CoV-2-Related Lung Inflammation Spreading by V:ERITAS (Vanvitelli Early Recognition of Inflamed Thoracic Areas Spreading).

Background Coronavirus disease 2019 (COVID-19) can be complicated by interstitial pneumonia, possibly leading to severe acute respiratory failure and death. Because of variable evolution ranging from asymptomatic cases to the need for invasive ventilation, COVID-19 outcomes cannot be precisely predicted on admission. The aim of this study was to provide a simple tool able to predict the outcome of COVID-19 pneumonia on admission to a low-intensity ward in order to better plan management strategies for these patients. Methods The clinical records of 123 eligible patients were reviewed. The following variables were analyzed on admission: chest computed tomography severity score (CTSS), PaO2/FiO2 ratio, lactate dehydrogenase (LDH), neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio, C-reactive protein (CRP), fibrinogen, D-dimer, aspartate aminotransferase (AST), alanine aminotransferase, alkaline phosphatase, and albumin. The main outcome was the intensity of respiratory support (RS). To simplify the statistical analysis, patients were split into two main groups: those requiring no or low/moderate oxygen support (group 1); and those needing subintensive/intensive RS up to mechanical ventilation (group 2). Results The RS intensity was significantly associated with higher CTSS and NLR scores; lower PaO2/FiO2 ratios; and higher serum levels of LDH, CRP, D-dimer, and AST. After multivariate logistic regression and ROC curve analysis, CTSS and LDH were shown to be the best predictors of respiratory function worsening. Conclusions Two easy-to-obtain parameters (CTSS and LDH) were able to reliably predict a worse evolution of COVID-19 pneumonia with values of >7 and >328 U/L, respectively.

Microsatellite Status Detection in Gastrointestinal Cancers: PCR/NGS Is Mandatory in Negative/Patchy MMR Immunohistochemistry.

BACKGROUND: Microsatellite instability (MSI) is a predictive biomarker for immune checkpoint inhibitors. The main goal was to investigate the discordance between IHC and PCR/NGS for MSI testing in gastrointestinal cancers. METHODS: Two series were analyzed through IHC for mismatch-repair-system proteins (MMRP) and PCR, with one series of 444 colorectal cancers (CRC) and the other of 176 gastric cancers (GC). All cases with discordant results between IHC and PCR were analyzed by NGS. IHC staining was evaluated as follows: proficient MMR (pMMR), with all MMR positive; deficient MMR (dMMR), with the loss of one heterodimer; and cases with the loss/patchy expression of one MMR (lo-paMMR). Cases with instability in at least two markers by PCR were MSI-high (MSI-H) and with instability in one marker, MSI-low (MSI-L). Cases without instability were evaluated as microsatellite-stable (MSS). RESULTS: In the CRC cohort, 15 out of 444 cases were dMMR and 46 lo-paMMR. Among the 15 dMMR, 13 were MSI-H and 2 MSS. Among the 46 lo-paMMR, 13 were MSI-H and 33 were MSS. In the GC cohort, 13 out of 176 cases were dMMR and 6 cases lo-paMMR. Among the 13 dMMR, 12 were MSI-H and only 1 was MSS. All six lo-paMMR cases were MSS. All NGS results were in agreement with PCR. CONCLUSIONS: In clinical practice, MMR-IHC could be used as a screening test and additional molecular analysis is mandatory exclusively in cases carrying loss/patchy MMR-IHC.

Behavior of circulating CD4+CD25+Foxp3+ regulatory T cells in colon cancer patients undergoing surgery.

CD4+CD25+Foxp3+ regulatory T cells (Treg) specialize in suppressing immune responses. In this study, 47 consecutive colon cancer patients were subjected to circulating Treg frequency assessment by flow cytometry before and after cancer resection. Thirty-two healthy subjects served as controls. Circulating Treg frequencies were significantly higher in colon cancer patients with respect to healthy controls. When patients were subgrouped according to Dukes stages, a linear relationship was observed between Dukes stages and Treg frequencies. In radically resected patients, Treg frequencies were shown to have significantly dropped down. Patients with advanced colon cancer were more likely to have significantly higher proportions of circulating Treg frequencies than Dukes A and B patients when compared to healthy subjects. Of note, nonradically resected patients were found to display reductions in-but not normalization of-Treg frequencies. These results suggest that cancer itself may be able to drive Treg recruitment as a strategy of immunoevasion.

Simultaneous non-functioning neuroendocrine carcinoma of the pancreas and extra-hepatic cholangiocarcinoma. A case of early diagnosis and favorable post-surgical outcome.

CONTEXT: Thanks to the wide use of diagnostic imaging modalities, multiple primary malignancies are being diagnosed more frequently and different associations of malignancies have been reported in this setting. CASE REPORT: In this paper, we describe the case of a patient with non-functioning well-differentiated neuroendocrine carcinoma of the head of the pancreas associated with extra-hepatic cholangiocarcinoma, in which an early diagnosis using magnetic resonance imaging allowed a good outcome. CONCLUSION: The simultaneous association of neuroendocrine pancreatic tumors and cholangiocarcinoma has not yet been described; however, this association should be considered and, due to the high contrast of magnetic resonance imaging, this technique is recommended in such patient in order to reach an accurate diagnosis.

Naples Prognostic Score Predicts Tumor Regression Grade in Resectable Gastric Cancer Treated with Preoperative Chemotherapy.

Despite recent progresses, locally advanced gastric cancer remains a daunting challenge to embrace. Perioperative chemotherapy and D2-gastrectomy depict multimodal treatment of gastric cancer in Europe, shows better results than curative surgery alone in terms of downstaging, micrometastases elimination, and improved long-term survival. Unfortunately, preoperative chemotherapy is useless in about 50% of cases of non-responder patients, in which no effect is registered. Tumor regression grade (TRG) is directly related to chemotherapy effectiveness, but its understanding is achieved only after surgical operation; accordingly, preoperative chemotherapy is given indiscriminately. Conversely, Naples Prognostic Score (NPS), related to patient immune-nutritional status and easily obtained before taking any therapeutic decision, appeared an independent prognostic variable of TRG. NPS was calculated in 59 consecutive surgically treated gastric cancer patients after neoadjuvant FLOT4-based chemotherapy. 42.2% of positive responses were observed: all normal NPS and half mild/moderate NPS showed significant responses to chemotherapy with TRG 1-3; while only 20% of the worst NPS showed some related benefits. Evaluation of NPS in gastric cancer patients undergoing multimodal treatment may be useful both in selecting patients who will benefit from preoperative chemotherapy and for changing immune-nutritional conditions in order to improve patient's reaction against the tumor.