[PANCREATIC NEUROENDOCRINE TUMORS (PNET): THE DILEMMA OF SURGERY VS. WATCHFUL WAITING APPROACH].

INTRODUCTION: Neuroendocrine tumors (NEN) originate from hormone producing cells located in various organs and tissues. NEN are unique tumors in terms of their diverse and particular clinical presentations, growth pattern, location and relatively good prognosis. NEN can be either secreting or non-secreting tumors. The clinical presentation and symptoms are according to the specific hormone produced by the tumor. A non-secreting tumor will eventually cause symptoms that relate to a mass-effect or a metastatic disease. There are various familial and genetic syndromes that are related to NEN. The most common neuroendocrine genetic syndrome is Multiple Endocrine Neoplasia syndrome type 1 (MEN 1). The clinical approach and treatment of NEN are unlike any other cancer. The gold standard management is surgery but unlike other cancerous diseases, surgical intervention is also indicated in cases of metastatic disease. There are several surgical approaches, and they all depend on tumor size, location, grade, stage, lymph node involvement, remote metastases and patients' age and comorbidities. Besides surgery, some cases are also treated with systemic therapies such as Somatostatin analogues, chemotherapy, immunotherapies, targeted therapies and occasionally radiation therapy is used. In the last decade there is a significant increase in the number of patients diagnosed with small non-secreting pancreatic tumors (PNET) due to advanced imaging techniques and diagnostic tools. This incidental increase is the reason for the emerging dilemma of whether to operate or merely conduct a watchful waiting policy. Small non-secreting tumors are commonly not considered malignant and thus the question is if surgery is always the right approach. The benefits of surgery must be carefully considered against the potential damage that may occur during these complex and radical procedures. Moreover, new and progressive systemic pharmacological therapies are now available to efficiently suppress tumor hormonal secretion. Recent studies have challenged surgery as the only treatment of choice, and in some cases suggest conservative treatment and follow up. The aim of this present literature review is to describe PNET diagnostic tools and evaluation, and to examine the different approaches of PNET treatment.

Signet Ring Cell Features are Associated with Poor Response to Neoadjuvant Treatment and Dismal Survival in Patients with High-Grade Esophageal Adenocarcinoma.

BACKGROUND: While the prognosis of patients with locoregional esophageal adenocarcinoma (EAC) has improved in the neoadjuvant treatment (NAT) era, high-grade histology (G3) is still associated with a limited treatment response. We sought to investigate oncologic outcomes in patients after esophagectomy for G3 EAC and to identify predictors of poor survival among these patients. METHODS: Patients with EAC who underwent resection with curative intent in 2011-2018 were divided by histologic grade (G3, G1/2) and compared for overall survival (OS). Cox regression was performed to analyze the response to NAT and the predictive role of signet ring cell (SRC) features. RESULTS: The cohort included 163 patients, 94 (57.7%) with G3 histology. NAT was administered to 69 (73.4%) patients. Following resection, OS in the G3 EAC group was 30 months (95% confidence interval [CI] 23.9-36.1). On univariate analysis, G3 disease (p = 0.050) and SRC features (p = 0.019) predicted low OS. Median survival in the G3 EAC group was worse in patients with SRC histology (18 months, 95% CI 8.6-27.4) than those without (30 months, 95% CI 23.8-36.1; p = 0.041). No patients with SRC histology were alive at 5 years of follow-up. Among all patients administered NAT, 88.2% of those with SRC showed minimal or no pathologic response and only 27.8% were downstaged. CONCLUSIONS: High-grade histology was found in most patients with EAC and predicted poor survival and treatment response. SRC features in patients with G3 disease were associated with lower OS. The benefit of NAT for G3 EAC in patients with SRC histology appears limited.

Teaching During the COVID-19 Pandemic: The Experience of the Faculty of Medicine at the Technion-Israel Institute of Technology.

BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic forced drastic changes in all layers of life. Social distancing and lockdown drove the educational system to uncharted territories at an accelerated pace, leaving educators little time to adjust. OBJECTIVES: To describe changes in teaching during the first phase of the COVID-19 pandemic. METHODS: We described the steps implemented at the Technion-Israel Institute of Technology Faculty of Medicine during the initial 4 months of the COVID-19 pandemic to preserve teaching and the academic ecosystem. RESULTS: Several established methodologies, such as the flipped classroom and active learning, demonstrated effectiveness. In addition, we used creative methods to teach clinical medicine during the ban on bedside teaching and modified community engagement activities to meet COVID-19 induced community needs. CONCLUSIONS: The challenges and the lessons learned from teaching during the COVID-19 pandemic prompted us to adjust our teaching methods and curriculum using multiple online teaching methods and promoting self-learning. It also provided invaluable insights on our pedagogy and the teaching of medicine in the future with emphasis on students and faculty being part of the changes and adjustments in curriculum and teaching methods. However, personal interactions are essential to medical school education, as are laboratories, group simulations, and bedside teaching.

Hazardous Postoperative Outcomes of Unexpected COVID-19 Infected Patients: A Call for Global Consideration of Sampling all Asymptomatic Patients Before Surgical Treatment.

BACKGROUND: In December 2019, a novel coronavirus was identified as the cause of many pneumonia cases in China and eventually declared as a pandemic as the virus spread globally. Few reports were published on the outcome of surgical procedures in diagnosed COVID-19 patients and even fewer on the surgical outcomes of asymptomatic undiagnosed COVID-19 surgical patients. We aimed to review all published data regarding surgical outcomes of preoperatively asymptomatic untested coronavirus disease 2019 (COVID-19) patients. METHODS: This report is a review on the perioperative period in COVID-19 patients who were preoperatively asymptomatic and not tested for COVID-19. Searches were conducted in PubMed April 4th, 2020. All publications, of any design, were considered for inclusion. RESULTS: Four reports were identified through our literature search, comprising 64 COVID-19 carriers, of them 51 were diagnosed only in the postoperative period. Synthesis of these reports, concerning the postoperative outcomes of patients diagnosed with COVID-19 during the perioperative period, suggested a 14/51 (27.5%) postoperative mortality rate and severe mostly pulmonic complications, as well as medical staff exposure and transmission. CONCLUSIONS: COVID-19 may have potential hazardous implications on the perioperative course. Our review presents results of unacceptable mortality rate and a high rate of severe complications. These observations warrant further well-designed studies, yet we believe it is time for a global consideration of sampling all asymptomatic patients before surgical treatment.

Laparoscopic hand-assisted liver resection for tumours in the left lateral section.

CONTEXT: The role of the laparoscopic left lateral sectionectomy (LLLS) is debatable, and Level-1 data are lacking. AIMS: The aim of the study is to evaluate the feasibility and safety of this approach. SETTINGS AND DESIGN: This was a retrospective study. SUBJECTS AND METHODS: From 2007 to 2014, patients undergoing LLLS were identified from two institutions. STATISTICAL ANALYSIS USED: Continuous variables were compared between groups with Student's t-test or Mann-Whitney test, as appropriate by type of distribution. Categorical variables were compared with Chi-square or Fisher's exact test, depending on the number of observations. RESULTS: Thirty-eight patients were included in the study. The mean age was 63.5 + 13 years (range, 31-89), and the mean number of tumours was 1.7 + 1.5. Eleven (29%) patients underwent LLS combined with an additional liver resection (combined resections group). The mean duration of the operation and the mean estimated blood loss were significantly decreased in the LLS group compared to the combined resection group (101 + 71 min vs. 208 + 98 min and 216 + 217 ml vs. 450 + 223 ml;P < 0.05 for both, respectively). The major complications rate was 8% and no mortality occurred. CONCLUSIONS: In a subset of carefully selected cases, LLLS may provide the benefits of laparoscopy. This does not appear to compromise perioperative morbidity rates. We believe that this approach may serve as a training platform for surgical trainees.

[INTRAOPERATIVE RADIOTHERAPY (IORT) IN EARLY BREAST CANCER - 500 PATIENTS, ONE CENTER'S EXPERIENCE].

AIMS: To present our Institute's experience with intraoperative radiotherapy in this selected population by collecting and analyzing clinical data, including long-term follow-up. BACKGROUND: Breast-conserving therapy is the standard treatment for early-stage breast cancer. The treatment includes tumor resection and a whole breast irradiation. Intraoperative radiotherapy is a single dose of irradiation given to the tumor bed immediately after it is removed. This treatment is suitable for a selected population of patients with early stage breast cancer, which constitutes about 20% of all breast cancer patients and is supposed to replace the standard whole breast radiation treatment. METHODS: Between the years 2006-2017, 737 women with early breast cancer were treated in Carmel Medical Center with intraoperative radiotherapy. We herein report the results of the first 500 patients who were treated until 2015. RESULTS: In 13.8% of the patients, additional breast treatment was recommended due to poor pathological characteristics of the disease in final pathological examination. During a median follow-up period of 74 months (1-136), recurrence was observed in 22 patients (4.4%), and in 7 patients (1.4%) recurrence was observed in regional lymph nodes; 13 patients (2.6%) developed metastatic disease. Risk factors for regional recurrence were identified: tumor size greater than 2 cm, lack of adjuvant therapy and poor genetic profile of the disease. CONCLUSIONS: Intraoperative radiotherapy is feasible and may offer an alternative to the standard whole breast radiotherapy, in low risk early breast cancer patients. The patients should be selected according to known risk factors.

The Impact of Surgeons: Pathologists Dialog on Lymph Node Evaluation of Colorectal Cancer Patients.

BACKGROUND: Lymph node (LN) retrieval and assessment is essential for accurate staging and treatment planning in colorectal cancer (CRC). According to U.S. National Cancer Institute recommendations, the minimal number of LNs needed for accurately staging of node-negative CRC is 12. Awareness and implementation of the guidelines has been shown to improve after assigning an opinion leader who has a special interest in CRC. OBJECTIVES: To evaluate the impact of dialogue between surgeons and pathologists in LN evaluation. METHODS: Consecutively treated CRC patients at the Department of Surgery B at Rambam Medical Center from January 1, 2000 through July 30, 2005 were identified from hospital discharge files. Demographic, surgical, and pathological data were extracted. Patients were divided into two groups. Group I patients underwent surgery before the initiation of a structured surgical oncology service (January 1, 2000 to October 30, 2004). Group II patients underwent surgery after the initiation of the service (November 1, 2004 to July 30, 2005). RESULTS: The study comprised 212 patients (Group I: n=170; Group II: n=42). The median number of LNs examined was 9 in Group I and 14 in Group II (P = 0.003). Only 35% of patients in Group I received adequate LN evaluation compared to 79% in Group II (P = 0.0001). Patients with left-sided or rectal cancer were less likely to receive adequate LN evaluation than patients with right-sided cancers. CONCLUSIONS: A durable improvement in LN evaluation was realized through a multi-pronged change initiative aimed at both surgeons and pathologists.

[OUTCOMES OF HEPATIC, PANCREATIC AND GASTRIC SURGERY IN THE ELDERLY POPULATION: MORBIDITY, MORTALITY AND RESPONSE TO ONCOLOGIC TREATMENT].

INTRODUCTION: There is a continuous rise in the proportion of elderly people in the general population. Previously, old age was a contraindication for numerous medical procedures. AIM: To assess the postoperative outcome of elderly patients who underwent major surgery of the liver, pancreas and stomach. MATERIALS AND METHODS: A retrospective analysis of patients aged 75 and older who underwent elective operations for malignant tumors of the stomach, pancreas and liver between January 2005 and December 2009 in the Department of Surgery A, at Carmel Medical Center. RESULTS: Of 258 operations, 80 (31%) were performed on patients older than 75 years; 46 (57.5%) were for males and 34 (42.5%) for females, with a mean age of 79 years. One patient was operated on twice. In 68 Patients (85%) the disease was primary and in 12 (15%) it was metastatic; 28 (35.4%) tumors were in the distal stomach, 13 (16.5%) in the proximal stomach; in the pancreas 13 tumors (16.5%) were in the head and 8 (10.1%) in the body/tail; 17 patients had liver metastases (21.5%1; 68 operations (85%) were performed in an open approach and 12 (15%) laparoscopically. Median hospital stay was 12 (±7.48) days and median ICU stay was 2 (±3.53) days. Median followup was 23 (±23) months. Complete records of 76 patients showed that 33 (43.4%) are alive with no evidence of disease; 12 (15.8%) were alive with stable disease; 25 (32.89%) died of cancer and 6 (7.8%) of other causes. DISCUSSION: These favorable results allow us to offer elderly patients the entire spectrum of surgical and medical procedures without considering advanced age as an absolute contraindication. CONCLUSIONS: Chronological age as a single parameter should not be a contraindication for radical medical treatment.

The Effects of Primary Tumor Location on Survival after Liver Resection for Colorectal Liver Metastasis in the Mediterranean Population.

(1) Background: There is an abundance of literature available on predictors of survival for patients with colorectal liver metastases (CRLM) but minimal information available on the relationship between the primary tumor location and CRLM survival. The studies that focus on the primary tumor location and CRLM survival exhibit a great deal of controversy and inconsistency with regard to their results (some studies show statistically significant connections between the primary tumor location and prognosis versus other studies that find no significant relationship between these two factors). Furthermore, the majority of these studies have been conducted in the West and have studied more diverse and heterogenous populations, which may be a contributing factor to the conflicting results. (2) Methods: We included patients who underwent liver resection for CRLM between December 2004 and January 2019 at two university-affiliated medical centers in Israel: Carmel Medical Center (Haifa) and Rabin Medical Center (Petach Tikvah). Primary tumors located from the cecum up to and including the splenic flexure were labeled as right-sided primary tumors, whereas tumors located from the splenic flexure down to the anal verge were labeled as left-sided primary tumors. (3) Results: We identified a total of 501 patients. Of these patients, 225 had right-sided primary tumors and 276 had left-sided primary tumors. Patients with right-sided tumors were significantly older at the time of liver surgery compared to those with left-sided tumors (66.1 + 12.7 vs. 62 + 13.1, p = 0.002). Patients with left-sided tumors had slightly better overall survival rates than those with right-sided tumors. However, the differences were not statistically significant (57 vs. 50 months, p = 0.37 after liver surgery). (4) Conclusions: The primary tumor location does not significantly affect patient survival after liver resection for colorectal liver metastasis in the Mediterranean population.

Short- and Long-Term Outcomes in Elderly Patients Following Hand-Assisted Laparoscopic Surgery for Colorectal Liver Metastasis.

(1) Background: Hand-assisted laparoscopic surgery (HALS) has engendered growing attention as a safe procedure for the resection of metastatic liver disease. However, there is little data available regarding the outcomes of HALS for colorectal liver metastasis (CRLM) in patients over the age of 75. (2) Methods: We compare the short- and long-term outcomes of patients >75-years-old (defined in our study as "elderly patients" and referred to as group 1, G1), with patients <75-years-old (defined in our study as "younger patients" and referred to as group 2, G2). (3) Results: Of 145 patients, 28 were in G1 and 117 were in G2. The most common site of the primary tumor was the right colon in G1, and the left colon in G2 (p = 0.05). More patients in G1 underwent laparoscopic anterior segment resection compared with G2 (43% vs. 39% respectively) (p = 0.003). 53% of patients in G1 and 74% of patients in G2 completed neoadjuvant therapy (p = 0.04). The median size of the largest metastasis was 32 (IQR 19-52) mm in G1 and 20 (IQR 13-35) mm in G2 (p = 0.001). The rate of complications (Dindo-Clavien grade ≥ III) was slightly higher in G1 (p = 0.06). The overall 5-year survival was 30% in G1 and 52% in G2 (p = 0.12). (4) Conclusions: Hand-assisted laparoscopic surgery for colorectal liver metastasis is safe and effective in an elderly patient population.

The Association between Preoperative Vitamin D Levels and Postoperative Complications in Patients Undergoing Colorectal Liver Metastasis Surgery.

(1) Background: Over the past several years, there has been a renewed interest with regard to the effect of pre-operative vitamin D levels on post-surgical outcomes. Pre-operative vitamin D deficiency has been associated with many negative post-operative outcomes. However, the role of vitamin D in postoperative outcomes in colorectal liver metastasis (CRLM) resection is relatively uninvestigated. Our study investigated the correlation between preoperative vitamin D levels and postoperative complications in patients undergoing resection for CRLM. (2) Methods: We retrospectively examined the post-operative course of 109 patients, who were evaluated based upon preoperative vitamin D levels: the first group had vitamin D levels less than 25 nmol/L (VIT D < 25 nmol/L) (n = 12) vs. the second group who had vitamin D levels equal to or greater than 25 nmol/L (VIT D ≥ 25 nmol/L) (n = 97). (3) Results: Patients with lower pre-operative vitamin D levels (VIT D < 25 nmol/L) had significantly higher rates of blood transfusions (33.3% vs. 10.3%, p = 0.01), post-operative surgical complications (50% vs. 17.5%, p = 0.009), and infectious complications (25% vs. 7.2%, p = 0.04). However, there was no difference in overall survival seen between the two groups. (4) Conclusions: The results of our study indicate that patients with preoperative vitamin D deficiency (defined as preoperative vitamin D levels less than 25 nmol/L) may have an increased risk of postoperative complications in patients undergoing liver surgery for metastatic colorectal cancer.

The Role of Preoperative Platelet-to-Lymphocyte Ratio as a Predictor for Incisional Hernias after Hand-Assisted Laparoscopic Liver Surgery for Metastatic Colorectal Cancer.

(1) Background: Hand-assisted laparoscopic surgery for liver resection is a globally established technique. In this study, we report on the incidence and risk factors for postoperative incisional hernia (IH) after hand-assisted laparoscopic surgery for colorectal liver metastasis. (2) Methods: This was retrospective analysis of 89 consecutive hand-assisted laparoscopic surgery for colorectal liver metastasis. (3) Results: Participants were 39 females and 50 males. Median age was 65 years, and in 63%, the BMI was ≥25. Postoperative complications were encountered in 18% of the patients. Seven patients (7.8%) had postoperative incisional hernia in the hand port site. There was significantly higher incidence of incisional hernia in overweight patients (BMI ≥ 25) (p = 0.04), and in cases with simultaneous liver and colon resection (p = 0.02). In univariant and multivariant analyses, simultaneous liver and colon resection (p = 0.004 and 0.03, respectively), and platelet-to-lymphocyte ratio ≤ 200 (p = 0.03, 0.04, respectively) were both independent risk factors for developing postoperative incisional hernia. (4) Conclusions: Both simultaneous liver and colon resection, and platelet-to-lymphocyte ratio ≤ 200 are independent risk factors for postoperative incisional hernia after hand-assisted laparoscopic surgery for colorectal liver metastasis.

Proteomic analysis to identify markers for response to neoadjuvant treatment in esophageal and gastroesophageal cancer.

BACKGROUND: Esophageal cancer represents a global challenge. Despite significant evolution of treatment protocols in the past decade, recurrence rates are still high and survival rates are poor. Current treatment paradigm for localized gastroesophageal junction (GEJ) carcinoma remains to be further elucidated as for the role of neoadjuvant chemoradiation versus perioperative chemotherapy. AIM: To identify biomarkers for response to chemoradiation in esophageal and gastroesophageal cancer, we performed an in-depth proteomic analysis of esophageal and gastroesophageal tumors, to describe differences in pathway activation between patients with favorable and poor prognosis following neoadjuvant chemoradiation. METHODS: Patients with locally advanced esophageal and gastroesophageal cancer following neoadjuvant chemoradiation were included in the cohort. The study cohort was dichotomized into two groups of patients, named "favorable prognosis" and "poor prognosis" according to the postoperative disease-free interval. We performed a mass spectrometry analysis of proteins extracted from the malignant regions of surgical specimens and analyzed data from electronic medical records. Clinical data was correlated with differences in protein expression between patient with a favorable and poor prognosis using validated gene expression pathways. RESULTS: The study included 35 patients with adenocarcinoma. All patients in this cohort had esophageal adenocarcinoma. Patients median age was 62 years. Twenty-five (71.3%) patients underwent neoadjuvant chemoradiation, and 28.7% underwent neoadjuvant chemotherapy only. A proteomic analysis of our cohort identified 2885 proteins. Enrichment levels of 98 of these proteins differed significantly between favorable and poor prognosis cohorts in patients who underwent neoadjuvant chemoradiation (p < .05) but not in patients who underwent neoadjuvant chemotherapy. The favorable prognosis patients group analysis exhibited differential enrichment of 87 proteins related to cellular respiration and oxidative phosphorylation pathways as well as proteins of the RAS oncogene family. CONCLUSION: In this study we identified differential enrichment of pathways related to oxidative phosphorylation and RAS oncogene pathway in esophageal cancer patients with a favorable response to chemoradiation. Following further validation, our findings may portray potential surrogate signature of biomarkers based upon these pathways.

Tumor Lymphocyte Infiltration Is Correlated with a Favorable Tumor Regression Grade after Neoadjuvant Treatment for Esophageal Adenocarcinoma.

(1) Background: We aimed to explore the association between neoadjuvant treatment, tumor-infiltrating immune lymphocyte (TIL), and tumor-associated macrophage (TAM) and survival in patients with esophageal adenocarcinoma. (2) Methods: Patients who underwent esophagectomy were divided into three groups according to their treatment modality and tumor regression grade (TRG): (i) surgery-only group (SG), (ii) good responders (GR) group (TRG 0−1), and (iii) bad responders (BR) group (TRG 2−3). We then carried out statistical correlations of the immunofluorescence analysis of the immune infiltrate in the esophageal surgical specimens with several clinical and pathological parameters. In addition, we analyzed The Cancer Genomic Atlas (TCGA) dataset for differences in TILs, TAMs, and protein expression in immune pathways. (3) Results: Forty-three patients (SG­15, GR­13, and BR­13) were evaluated. The highest enrichment of CD3+ (p < 0.001), CD8+ (p = 0.001) and CD4+ (p = 0.009) was observed in the stroma of GR patients. On multivariate analysis, only CD8+ T cell and signet-ring features were independent prognostic factors for overall survival. In TCGA analysis, we identified overexpression of TAM and colony-stimulating factor 1 receptor (CSF-1R). (4) Conclusions: High enrichment of lymphocyte subpopulations in the microenvironment of esophageal adenocarcinoma is associated with a favorable response to neoadjuvant treatment and an improved patient outcome.

Resection of Primary Renal Leiomyosarcoma Involving the Inferior Vena Cava (IVC) with IVC Resection and Reconstruction.

Renal leiomyosarcoma is a rare, aggressive tumor of the smooth muscles of the kidney. In our case, the tumor has special characteristics that made it highly challenging, as it involved major vessels and other adjacent vital structures. The rarity of the tumor type itself and the special challenging features we faced intraoperatively encouraged us to report the case including the management plan for R0 resection. Our patient is a forty-two years old previously healthy female, with vague nonspecific presenting complains, ended up with a major highly advanced surgery necessitating the need for vascular reconstruction of IVC. The surgery was performed by a multidisciplinary team of highly specialized surgeons in related fields. The surgery went well, and the outcome was promising. The patient was followed up for about four months later, with uneventful course.

Hand-Assisted Laparoscopic Surgery Is Superior to Open Liver Resection for Colorectal Liver Metastases in the Posterosuperior Segments.

Introduction: Laparoscopic liver resections (LLR) of colorectal metastasis located in posterosuperior segments (1, 4A, 7 and 8) are challenging and highly demanding. The aim of our study is to determine the safety and feasibility of hand-assisted laparoscopic surgery (HALS) in the resections of the posterosuperior lesions and to compare the peri-operative, short-term and long-term outcomes with the open liver resection (OLR) approach. Methods and Results: A retrospective study of patients who underwent either HALS or OLR for metastatic colorectal cancer (mCRC) located in the posterosuperior segments of the liver between 2008 and 2018 in two university affiliated medical centers. Results: A total of 187 patients were identified, of whom 78 underwent HALS and 109 underwent OLR. There was no difference between the HALS and OLR with regard to preoperative factors (age, primary CRC tumor location, number and anatomical distribution of liver metastasis, pre-operative neo-adjuvant treatment, operative time, blood transfusion rate, and resection margins positivity). On the other hand, HALS compared to OLR had a significantly shorter mean hospital stay (4 vs. 6 days; P = 0.003), and a lower total complications rate (25 vs. 47% P = 0.006). Both groups had no 30-day mortality. Also, patients who underwent HALS vs. OLR had similar liver metastases recurrence (55 vs. 51%. P = 0.65) and 5-year survival (47 vs. 45%. P = 0.72). Conclusions: HALS for mCRC located in posterosuperior liver segments is safe and feasible and it is a preferable approach due to its lower complication rate and shorter hospital stay while not compromising survival and disease recurrence.

Laparoscopic Versus Open Simultaneous Resection of Primary Colorectal Cancer and Associated Liver Metastases: A Comparative Retrospective Study.

PURPOSE: The aim was to compare the short-term and long-term outcomes of patients with metastatic colorectal cancer (CRC) undergoing laparoscopic versus open colorectal resection with simultaneous resection for liver metastases. Currently there is a lack of studies that have investigated the oncosurgical aspects and the short and long-term outcomes from these procedures. MATERIALS AND METHODS: A retrospective study of patients who underwent simultaneous resections for CRC and synchronous liver metastases between 2008 and 2019 in 2 university affiliated medical centers. RESULTS: Sixty-three patients were identified of whom 21 had successful laparoscopic simultaneous resections. In 43% of patients, the primary tumor was located in the right colon. The 3-year overall survival and disease-free survival rates were 87% and 48%, respectively. When compared with a separate control group of 42 patients who underwent conventional open resections, the laparoscopic approach was associated with an increased operative time (286 vs. 225 min, P=0.05), but a shorter hospital stay (6 vs. 8 d, P=0.008). CONCLUSIONS: Simultaneous laparoscopic colorectal and parenchymal sparing liver resection for metastatic CRC is safe, feasible, and it is a preferable approach because of better short-term outcome compared with open surgery while not compromising survival and disease recurrence.

Hand-assisted Laparoscopic Surgery for Colorectal Liver Metastasis: Analysis of Short-term and Long-term Results.

BACKGROUND: There is scant data regarding the outcomes of hand-assisted laparoscopic surgery (HALS) for colorectal liver metastasis (CRLM). The aim of this study is to report our experience and analyze the short-term and long-term results. MATERIALS AND METHODS: Retrospective study of patients undergoing HALS for CRLM in 2 university affiliated medical centers. RESULTS: Two hundred and thirty-eight liver procedures were performed on 145 patients including 205 parenchymal sparing resections and 33 anatomic resections. The median number of metastases was 1 (range: 1 to 8), 38 patients (26.2%) had 3 or more metastases, and 41 patients (28.3 had a bi-lobar disease. The tumor size was 20 (2 to 90) mm, and 52 patients (36.6%) had a tumor larger than 30 mm. Nighty-nine patients (67.8%) received neoadjuvant chemotherapy. In 8 patients (5.5%) the laparoscopic liver resection was combined with ablation, and 16 patients (11%) underwent a synchronous resection of colorectal cancer. The median operative time, blood loss during surgery, and postoperative hospital stay were 163 minutes, 300 mL, and 4 days, respectively. The median modified Iwate complexity score was 4 (0 to 10) and the conversion rate to open surgery was 5.5%. The overall and major complication rates were 23.8% and 3.6%, respectively. The mortality rate was 0.7%. R0 resections were achieved in 91% of patients. Median overall survival for all the cohort (intend to treat) was 59 months, and the 8- and 10-year overall survival rates were 47.3% and 24.9%, respectively. CONCLUSIONS: This study shows that HALS is a safe and efficacious treatment for selected patients with CRLM.

ERBB2 Pathway in Biliary Tract Carcinoma: Clinical Implications of a Targetable Pathway.

BACKGROUND/AIMS: Current chemotherapy regimens for cholangiocarcinoma (CCA) yield poor outcomes, with a median overall survival of <12 months. Recent data on the genomic landscape of CCAs have created opportunities for targeted therapy. Yet, data regarding its efficacy are scarce. We aimed to describe the genomic landscape of a CCA patient cohort using next-generation sequencing (NGS), focusing on the ERBB/EFGR pathway and assessing response to anti-HER2 agents. METHODS: Tissue samples of intrahepatic CCA (IHCC) and extrahepatic CCA (EHCC) underwent NGS for somatic aberrations. The clinical outcomes for patients treated with anti-HER2 agents were evaluated. RESULTS: A total of 1,863 CCA cases (1,615 IHCCs and 248 EHCCs) underwent NGS, and they revealed a high prevalence of ERBB alterations (IHCC, 4.2%; EHCC, 9.7%). Among these, 23.8% of the IHCCs and 53.6% of the EHCCs had a point mutation in ERBB2, and 66.6% of the IHCCs and 41.2% of the EHCCs had ERBB copy number amplification. Three EHCC patients were diagnosed at our institute with ERBB/EGFR aberrations; 2 patients were treated with neratinib and 1 patient with a chemotherapy-trastuzumab combination. All 3 achieved disease stabilization and a clinical benefit. One patient underwent a liquid biopsy before and after 3 months of treatment, demonstrating disappearance of the ERBB2 clone and emergence of a Myc-mutated clone after treatment. CONCLUSIONS: The genomic landscape of CCAs may harbor targetable alterations, especially in the ERBB/EGFR pathway. These alterations may have clinical significance in everyday practice.