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Objective: To determine whether sarcopenia can potentially predict worse survival after resection of pancreatic ductal adenocarcinoma. Background: Sarcopenia is correlated with poor outcomes in hepatopancreatobiliary malignancies, but the relationship of both its qualitative and quantitative features with patient survival after pancreatectomy has not been investigated in a western population. Patients and Methods: Preoperative cross-sectional computed tomography scans of consecutive patients who underwent pancreatectomy in 2005–2017 were evaluated for skeletal muscle index (SMI), intramuscular adipose tissue content (IMAC), and visceral-to-subcutaneous adipose tissue area ratio (VSR). Sex-specific categorical cut-offs were determined. Findings were correlated with outcome. Results: The study included 111 patients, 47% of whom were female, with a median age of 67 years (range: 35–87 years), and median body mass index of 23 kg/m2 (range: 16–40 kg/m2); 77% had a Whipple procedure and 66% received adjuvant chemotherapy. Low SMI correlated with poor overall survival (OS) (P = 0.007), disease-specific survival (DSS) (P = 0.006), and recurrence-free survival (RFS) (P = 0.01). High IMAC correlated with poor OS (P = 0.04). Patients with high IMAC tended to have a shorter DSS (P = 0.09), with no correlation with RFS (P = 0.6). VSR was not associated with survival. Multivariable analysis yielded an independent association of low SMI with OS (HR = 1.7, 95%CI: 1.1–2.8, P = 0.02), DSS (HR = 1.8, 95%CI: 1.03–3.2, P = 0.04), and RFS (HR = 1.8, 95%CI: 1.1–2.8, P = 0.01), and of high IMAC with OS (HR = 1.9, 95%CI: 1.1–3.1, P = 0.01). Conclusion: Both qualitative and quantitative measures of skeletal muscle were independently associated with impaired survival in patients with resectable PDAC. Sarcopenia might serve as an early radiographic surrogate of aggressive tumor behavior, with potential implications for clinical decision-making and future 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.

Studies have suggested that neutrophil-to-lymphocyte ratio (NLR) has value as a predictor of long-term outcomes in various cancer types. Its prognostic potential in patients with CRLM has not been thoroughly investigated. This original, retrospective study assessed the relationship between the preoperative NLR, survival outcomes, and recurrence patterns in patients after colorectal liver metastasis resection (CRLM). The prospectively maintained database of a tertiary medical center was queried for all patients who underwent CRLM resection between 2005 and 2017. Patients were divided into two groups: NLR 3 (high). Recurrence risk was analysed using Fine and Gray correction for competing risk method and cause specific analyses. The cohort included 231 patients of whom 53 (23%) had a high neutrophil-to-lymphocyte ratio. At presentation, 35% had synchronous disease and 48% had a solitary metastasis; median tumor size was 2 cm. Patients with a high NLR had a significantly higher rate of simultaneous colorectal resection (P = 0.01). A high NLR was independently associated with worse OS (P = 0.02), worse DFS (P = 0.03), and higher risk of recurrence (P = 0.048), specifically recurrence with an extrahepatic pattern (P = 0.03). A high preoperative NLR was independently associated with poorer survival outcomes and extrahepatic recurrence pattern. The NLR appears to have prognostic importance in CRLM and may serve as a surrogate marker of aggressive systemic disease after resection. These findings warrant external validation, preferably in a prospective design.

Background: Transanal endoscopic microsurgery (TEM) is considered the procedure of choice for rectal adenomas non-amendable for endoscopic excision and for early rectal cancer. TEM may gain more importance in patients who are considered unfit for major surgery. The option of spinal anaesthesia may offer many advantages for patients undergoing TEM while maintaining the principles of complete tumour excision. The aim of this study is to report the outcome of patients undergoing TEM under spinal anaesthesia. Methods: Demographic and clinical data pertaining patients undergoing TEM under spinal anaesthesia between 2004 and 2015 were retrospectively collected. Results: A total of 158 TEM procedures were recorded in the study period. Twenty-three patients (15%) underwent the procedure under spinal anaesthesia and were included in the study; 13 of them were male and ten were female. The mean age of the patients was 69.1 ± 10.6 years. Seventeen (74%) rectal lesions were adenomas, two (9%) were adenocarcinoma and four (17%) had involved margins after polypectomy. The mean tumour size was 2.1 cm (range, 0.5–3). Distance from the anal verge was 7.7 ± 2.2 cm. Seventeen (74%) lesions were in the posterior wall. The operative time was 73 min (range, 46–108) No adverse anaesthesia-related events were recorded, and the post-operative pain was reduced. The median time of hospitalisation was 2 days (range, 1–4). No major complications were noted, and the minor complications were treated conservatively. The surgical margins were free of tumour in all cases. Conclusion: TEM under spinal anaesthesia had short duration of surgery, no increase in operative and post-operative complications or hospital length of stay. Avoiding the use of general anaesthesia, in such challenging procedure, may open new opportunities for patients determined to be unfit for general anaesthesia.

810 Background: Frailty is associated with increased postoperative complications. Despite multiple evidence-based modalities to assess frailty, surgeons often make subjective assessments of patients’ ability to tolerate surgery. Identification of those at risk of poor outcomes is particularly important in Surgical Oncology, as major resections may worsen debility and functional status, limiting the patients' ability to receive further therapy. The Risk Analysis Index (RAI-C) is a validated tool to assess frailty in surgical patients. It assigns points for any cancer diagnosis, potentially overestimating frailty in Surgical Oncology patients, and has not been validated in this subgroup. Methods: We performed a prospective, surgeon-blinded study to correlate results of a preoperatively administered frailty survey to predict short- and long-term outcomes in patients with histologically proven malignancy who underwent surgery. The RAI-C, Patient Health Questionnaire (PHQ9), and General Anxiety Disorder (GAD) surveys were administered to assess for frailty, depression, and anxiety, respectively; C-reactive protein (CRP), pre-albumin, albumin, and hematocrit were obtained. Outcomes, including readmission, major complications, ICU admission, disposition (home vs rehabilitation/nursing facility), and 1-year survival were compared between the different groups as defined by survey and lab results. Results: One hundred ninety-one patients were included, of which 135 patients were considered frail based on the predefined value (RAI-C ≥21). Frail patients were more likely to be readmitted within 30 days (14% vs 2%, P=0.01). No difference was found in length of stay, 90-day readmission, ICU admission, major complications, or disposition. Only 15.8% of patients met criteria for anxiety and 11% met criteria for depression. Measured outcomes were similar in patients defined as anxious or depressed. Patients with abnormal pre-albumin levels were more likely to require ICU admissions (31% vs 8%, P

Gallbladder cancer accounts for 1.2% of global cancer diagnoses. Literature on biliary-type adenocarcinoma (BTA), and specifically carcinoma arising from intracholecystic papillary-tubular neoplasms (ICPNs), is limited. This study describes a retrospective, single-institution experience with gallbladder cancer, focusing on histological subtypes and prognosis.A retrospective review was performed of patients who underwent cholecystectomy for a malignant neoplasm of the gallbladder between 2007 and 2017. Demographic, clinicopathologic, and operative variables, as well as survival outcomes, were analyzed.From a total of 145 patients, BTAs were most common (93, 64%). Compared with non-BTAs, BTAs were diagnosed at a lower American Joint Committee on Cancer stage (p = 0.045) and demonstrated longer median recurrence-free survival (38 vs. 16 months, p = 0.014; median follow-up 36 months). Tumors arising from ICPNs (18, 12%) were more commonly associated with BTA (14 cases). Compared with BTAs not associated with ICPNs (29 patients), associated cases demonstrated lower pathologic stage (p = 0.006) and lower rates of liver and perineural invasion (0% vs. 49% and 14% vs. 48%, respectively; p 0.05). Cumulative 5-year survival probability was higher for patients with gallbladder neoplasm of any subtype associated with ICPNs compared with those that were not associated with ICPNs (54% vs. 41%, p = 0.019; median follow-up 23 months). This difference was also significant when comparing BTAs associated with ICPNs and non-associated cases (63% vs. 52%, p = 0.005).This study demonstrated unique pathological and prognostic features of BTAs and of carcinomas arising from ICPNs. Histopathological variance may implicate prognosis and may be used to better guide clinical decision making in the treatment of these patients.

Surgical myotomy is the best therapeutic option for patients with achalasia. The minimally invasive technique is considered to be the preferred method for many surgeons. Robotic-assisted laparoscopic myotomy has several advantages over conventional laparoscopic surgery. These benefits include more accurate incisions that may result in a lower rate of intra-operative complications.To describe our technique of performing robotic-assisted Heller myotomy and to review the initial results of this procedure.All patients undergoing robotic-assisted Heller myotomy for achalasia between the years 2012-2018 at Rabin Medical Center were retrospectively reviewed from our institutional prospective database.Thirty patients underwent robotic-assisted Heller myotomy for achalasia. Mean operative time was 77 minutes (range 47-109 minutes) including docking time of the robotic system. There were no cases of conversion to laparoscopic or open surgery. There were no cases of intra-operative perforation of the mucosa. None of the patients had postoperative morbidity or mortality. Good postoperative results were achieved in 25 patients. Four patients required additional intervention (3 had endoscopic dilatations and 1 with known preoperative endstage achalasia had undergone esophagectomy). One patient was lost to follow-up.Robotic-assisted Heller myotomy is a safe technique with a low incidence of intra-operative esophageal perforation compared to the laparoscopic approach. We believe that robotic-assisted surgery should be the procedure of choice to treat achalasia.

Background Hand-assisted laparoscopic surgery is a widely accepted alternative to an open approach. The use of this technique in repeat liver resection is limited due to technical difficulties caused by postsurgical adhesions. We aimed to assess the feasibility and safety of hand-assisted laparoscopic repeat hepatectomy (HALRH). Materials and methods This was a retrospective study of the medical files of patients who had undergone HALRH between 2010 and 2017 in 2 university-affiliated medical centers. Results Sixteen patients with repeat hepatectomy were included with a median age of 67.5 years. The first liver resection was a traditional laparotomy for 9 patients and hand-assisted laparoscopic surgery for 7 patients. The conversion rate to open surgery was 6%. The median operative time, blood loss during surgery, and postoperative hospital stay were 166 minutes, 400 mL, and 7 days, respectively. R0 resections were achieved in 88% of patients. The median number of tumors and tumor size were 1 and of 25 mm, respectively. There were no mortalities or major complications postoperatively. For patients with colorectal liver metastases, the median follow-up and overall survival were 21 and 43 months, respectively. Conclusion The findings suggest HALRH to be safe and feasible. Future ERAS guidelines should evaluate this approach for liver surgery.

To determine whether sarcopenia can potentially predict worse survival after resection of pancreatic ductal adenocarcinoma.Sarcopenia is correlated with poor outcomes in hepatopancreatobiliary malignancies, but the relationship of both its qualitative and quantitative features with patient survival after pancreatectomy has not been investigated in a western population.Preoperative cross-sectional computed tomography scans of consecutive patients who underwent pancreatectomy in 2005-2017 were evaluated for skeletal muscle index (SMI), intramuscular adipose tissue content (IMAC), and visceral-to-subcutaneous adipose tissue area ratio (VSR). Sex-specific categorical cut-offs were determined. Findings were correlated with outcome.The study included 111 patients, 47% of whom were female, with a median age of 67 years (range: 35-87 years), and median body mass index of 23 kg/mBoth qualitative and quantitative measures of skeletal muscle were independently associated with impaired survival in patients with resectable PDAC. Sarcopenia might serve as an early radiographic surrogate of aggressive tumor behavior, with potential implications for clinical decision-making and future study.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer, which commonly metastasizes to the liver. The current standard of care for metastatic PDAC is systemic chemotherapy, however there are limited emerging data regarding surgical resection of pancreatic oligometastases in select patients. Here we review the literature addressing resection of PDAC liver oligometastases.

Studies have suggested that neutrophil-to-lymphocyte ratio (NLR) has value as a predictor of long-term outcomes in various cancer types. Its prognostic potential in patients with CRLM has not been thoroughly investigated. This original, retrospective study assessed the relationship between the preoperative NLR, survival outcomes, and recurrence patterns in patients after colorectal liver metastasis resection (CRLM).The prospectively maintained database of a tertiary medical center was queried for all patients who underwent CRLM resection between 2005 and 2017. Patients were divided into two groups: NLR3 (normal) or3 (high). Recurrence risk was analysed using Fine and Gray correction for competing risk method and cause specific analyses.The cohort included 231 patients of whom 53 (23%) had a high neutrophil-to-lymphocyte ratio. At presentation, 35% had synchronous disease and 48% had a solitary metastasis; median tumor size was 2 cm. Patients with a high NLR had a significantly higher rate of simultaneous colorectal resection (P = 0.01). A high NLR was independently associated with worse OS (P = 0.02), worse DFS (P = 0.03), and higher risk of recurrence (P = 0.048), specifically recurrence with an extrahepatic pattern (P = 0.03).A high preoperative NLR was independently associated with poorer survival outcomes and extrahepatic recurrence pattern. The NLR appears to have prognostic importance in CRLM and may serve as a surrogate marker of aggressive systemic disease after resection. These findings warrant external validation, preferably in a prospective design.

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.

Aim This study examined the impact of the routine pneumococcal conjugate vaccination (PCV) on childhood community-acquired bacteraemia (CAB) and antibiotic resistance patterns in Israeli children. Methods Israel added the PCV vaccine to its national immunisation programme in July 2009. We retrospectively analysed the medical records of all patients with CAB under 18 years at three children's hospitals in Tel Aviv and Jerusalem from 2007 to 2015. The microbiological data, clinical presentation, pneumococcal serotype distribution, antibiotic susceptibility and outcomes of infections were compared before and after the vaccine was introduced. Results There were 511 904 emergency department visits and 125 922 children were hospitalised. Of those, 238 had CAB before vaccination was introduced (mean age 17 months) and 316 had CAB after the introduction (mean age 21 months). Emergency department presentations for CAB fell from 141.8 to 91.8 per 100 000 visits: a relative risk reduction (RRR) of 35%. Hospitalisations for CAB decreased from 430 to 337 per 100 000 admissions: an RRR of 22%. Hospitalisations due to Staphylococcus aureus increased significantly and penicillin nonsusceptible blood Streptococcus pneumoniae isolates decreased significantly. Conclusion Introducing national pneumococcal conjugate vaccination significantly changed the epidemiology of CAB, with reduced antibiotic-resistant Streptococcus pneumoniae and increased hospitalisation rates for Staphylococcus aureus infections.

Plant architecture is a predictable but flexible trait. The timing and position of organ initiation from the shoot apical meristem (SAM) contribute to the final plant form. While much progress has been made recently in understanding how the site of leaf initiation is determined, the mechanism underlying the temporal interval between leaf primordia is still largely unknown. The Arabidopsis ZRIZI (ZRZ) gene belongs to a large gene family encoding multidrug and toxic compound extrusion (MATE) transporters. Unique among plant MATE transporters identified so far, ZRZ is localized to the membrane of a small organelle, possibly the mitochondria. Plants overexpressing ZRZ in initiating leaves are short, produce leaves much faster than wild-type plants and show enhanced growth of axillary buds. These results suggest that ZRZ is involved in communicating a leaf-borne signal that determines the rate of organ initiation.

Leaves are formed at the flanks of the shoot apical meristem (SAM) and develop into a variety of forms. In tomato, prolonged leaf patterning enables the elaboration of compound leaves by reiterative initiation of leaflets with lobed margins. In goblet (gob) loss-of-function mutants,primary leaflets are often fused, secondary leaflets and marginal serrations are absent, and SAMs often terminate precociously. We show that GOBencodes a NAC-domain transcription factor expressed in narrow stripes at the leaf margins, flanking the distal side of future leaflet primordia, and at the boundaries between the SAM and leaf primordia. Leaf-specific overexpression of the microRNA miR164, a negative regulator of GOB-like genes,also leads to loss of secondary-leaflet initiation and to smooth leaflet margins. Plants carrying a dominant gob allele with an intact ORF but disrupted miR164 binding site produce more cotyledons and floral organs, have split SAMs and, surprisingly, simpler leaves. Overexpression of a form of GOB with an altered miR164 binding site in leaf primordia leads to delayed leaflet maturation, frequent, improperly timed and spaced initiation events, and a simple mature leaflet form owing to secondary-leaflet fusion. miR164 also affects leaflet separation in Cardamine hirsuta, a Brassicaceae species with complex leaves. Genetic and molecular analyses suggest that GOB expression is intact in the simplified leaves of entire tomato mutants, which have a defect in a putative repressor of auxin responses. Our results show that GOB marks leaflet boundaries and that its accurate spatial, temporal and quantitative activity affects leaf elaboration in a context-dependent manner.

Background The 7-valent pneumococcal conjugate vaccine (PCV7) has been part of the national vaccination program (NVP) in Israel since July 2009, and was replaced by 13-valent pneumococcal conjugate vaccine (PCV13) by November 2010. The current study was performed to determine the impact of routine pneumococcal vaccination on patterns in community-acquired bacteremia (CAB) in the Pediatric population in Israel. Methods Retrospective chart review of children aged 0–18 years that arrived to three tertiary care pediatric hospitals between January 2007 and December 2015 with CAB. Patients` charts were retrieved for demographic, clinical and microbiological data, final diagnoses and outcome. Results 554 children were included. Significant reduction was found in admission rate due to pneumococcal bacteremia (from 250.4/100,000 to 115.2/100,000; 54% reduction), lower respiratory infections (from 142.1/100,000 to 80.9/100,000; 43% reduction) and CAB (from 430 /100,000 to 337 /100,000; 22% reduction) p value < 0.0001 for all of them. Streptococcus pneumoniae was the most common pathogen in both periods, isolated in 258(46.6%) of cases. The relative proportion of S. pneumoniae decreased in the post-Prevnar period (from 60.9% to 35.5% P < 0.0001), while that of other pathogens increased, including Staphylococcus aureus (7.1% to 15.7%, P < 0.05) and Streptococcus pyogenes (3.4% to 6.9%, P < 0.05). The frequency of penicillin non-susceptible S. pneumoniae isolates decreased significantly (from 5.1% to 3.6%, P < 0.05). 86% (117/136) of the pneumococci isolated in the pre- prevnar period were PCV7 or PCV13 serotypes, compared with 50% (55/110) in the post- prevnar period. Meningitis was the final diagnosis in 31(5.6%) of patients, of them 18 (58.1%) were of pneumococcal meningitis,nine (50%) in the pre-Prevnar period. Overall mortality rate following CAB was 0.36%. Conclusion we demonstrate that PCV reduces pediatric morbidity and hospitalization rate and impacts epidemiology of CAB. These changes may require change in the empiric antimicrobial treatment of suspected bacteremia. Continued etiological surveillance is important. Disclosures All authors: No reported disclosures.

Class 1 KNOTTED1-LIKE HOMEOBOX (KNOXI) genes encode transcription factors that are expressed in the shoot apical meristem (SAM) and are essential for SAM maintenance. In some species with compound leaves, including tomato (Solanum lycopersicum), KNOXI genes are also expressed during leaf development and affect leaf morphology. To dissect the role of KNOXI proteins in leaf patterning, we expressed in tomato leaves a fusion of the tomato KNOXI gene Tkn2 with a sequence encoding a repressor domain, expected to repress common targets of tomato KNOXI proteins. This resulted in the formation of small, narrow, and simple leaves due to accelerated differentiation. Overexpression of the wild-type form of Tkn1 or Tkn2 in young leaves also resulted in narrow and simple leaves, but in this case, leaf development was blocked at the initiation stage. Expression of Tkn1 or Tkn2 during a series of spatial and temporal windows in leaf development identified leaf initiation and primary morphogenesis as specific developmental contexts at which the tomato leaf is responsive to KNOXI activity. Arabidopsis thaliana leaves responded to overexpression of Arabidopsis or tomato KNOXI genes during the morphogenetic stage but were largely insensitive to their overexpression during leaf initiation. These results imply that KNOXI proteins act at specific stages within the compound-leaf development program to delay maturation and enable leaflet formation, rather than set the compound leaf route.

Endo-beta-mannanase is one of the key enzymes involved in the hydrolysis of the mannan-rich cell walls of tomato (Solanum lycopersicon) seeds. Two isoforms of endo-beta-mannanase have been characterized in tomato seeds: LeMAN2 is active in the micropylar area prior to germination and LeMAN1 is active after germination in all endosperm cells surrounding the cotyledons. To explore whether general mannanase activity in the endosperm cap is sufficient to promote germination, the gene encoding LeMAN3 was inserted into transgenic tomato plants under the control of a CaMV-35S promoter. Expression of LeMAN3 was evident in the endosperm cap and in the lateral endosperm of the transgenic seeds 10 min after imbibition. An activity test indicated increased activity of endo-beta-mannanase in the transgenic lines relative to the control line in all seed parts, during the first 20 h of imbibition. However, overexpression of LeMAN3 in transgenic seeds inhibited seed germination at both optimal and suboptimal temperatures. Detailed RT-PCR analyses revealed the transcription patterns of the genes encoding the various mannanase isoforms, and indicated a delay in LeMAN2 transcription in the endosperm cap of the transgenic seeds. Interestingly, tissue-print assays indicated similar mannanase activity in the micropylar areas for both transgenic and control seeds. These results indicate that overexpression of active endo-beta-mannanase in the endosperm cap is not sufficient to enable hydrolysis of the cell walls or to promote germination of tomato seeds. Cell-wall hydrolysis in these endosperm cells is under tight control and requires the specific activity of LeMAN2.