Thoracic Duct Visualization in Esophageal Resection: A Pilot Trial.

INTRODUCTION: Inadvertent thoracic duct injury is common during esophagectomy and may result in postoperative chylothorax. This study's objective was to investigate utility of patent blue injection as a modality for intraoperative thoracic duct visualization. METHODS: A prospective, single-arm, interventional study of patients undergoing minimally invasive esophagectomy was performed. Patients were injected with patent blue dye into both groins prior to thoracic stage of surgery and assessed for duct visualization. Control group was formed by propensity score matching using retrospectively collected data regarding patients who underwent esophagectomy. RESULTS: A total of 25 patients were included in analysis, compared to a control of 50 patients after matching. Thoracic duct was visualized in 60% of patients in the study group (15/25 patients). Significant differences were found between study and control groups (p < 0.05) with regards to median operative time (422 vs. 285 min, respectively), overall complications (16 vs. 34%, respectively), and median postoperative length of stay (13.5 vs. 10 days, respectively). There was a difference in rate of chyle leak between study and control groups; however, this was not significant (0 vs. 12%, respectively, p = 0.17). CONCLUSION: Patent blue injection represents a simple method for thoracic duct visualization during minimally invasive esophagectomy which may improve surgical outcomes.

Major Postoperative Complications Limit Adjuvant Therapy Administration in Patients Undergoing Pancreatoduodenectomy for Distal Cholangiocarcinoma or Pancreatic Ductal Adenocarcinoma.

INTRODUCTION: Guidelines for perioperative systemic therapy administration in patients undergoing pancreatoduodenectomy for pancreatic adenocarcinoma (PDAC) and distal cholangiocarcinoma (dCCA) are evolving. Decisions regarding adjuvant therapy are influenced by postoperative morbidity, which is common after pancreatoduodenectomy. We evaluated whether postoperative complications are associated with receipt of adjuvant therapy after pancreatoduodenectomy. METHODS: A retrospective analysis of patients undergoing pancreatoduodenectomy for PDAC or dCCA from 2015 to 2020 was conducted. Demographic, clinicopathologic, and postoperative variables were analyzed. RESULTS: Overall, 186 patients were included-145 with PDAC and 41 with dCCA. Postoperative complication rates were similar for both pathologies (61% and 66% for PDAC and dCCA, respectively). Major postoperative complications (MPCs), defined as Clavien-Dindo >3, occurred in 15% and 24% of PDAC and dCCA patients, respectively. Patients with MPCs received lower rates of adjuvant therapy administration, irrespective of primary tumor (PDAC: 21 vs. 72%, p = 0.008; dCCA: 20 vs. 58%, p = 0.065). Recurrence-free survival (RFS) was worse for patients with PDAC who experienced an MPC [8 months (interquartile range [IQR] 1-15) vs. 23 months (IQR 19-27), p < 0.001] or who did not receive any perioperative systemic therapy [11 months (IQR 7-15) vs. 23 months (IQR 18-29), p = 0.038]. In patients with dCCA, 1-year RFS was worse for patients who did not receive adjuvant therapy (55 vs. 77%, p = 0.038). CONCLUSION: Patients who underwent pancreatoduodenectomy for either PDAC or dCCA and who experienced an MPC had lower rates of adjuvant therapy and worse RFS, suggesting that clinicians adopt a standard neoadjuvant systemic therapy strategy in patients with PDAC. Our results propose a paradigm shift towards preoperative systemic therapy in patients with dCCA.

T1 Gastric Cancer Is Associated With a High Incidence of Regional Lymph Node Metastases.

INTRODUCTION: Early stage gastric cancer, particularly T1 disease, is associated with high recurrence-free and overall survival rates following resection with curative intent. However, rare cases of T1 gastric cancer have nodal metastasis and this is associated with poor outcomes. METHODS: Data from gastric cancer patients treated with surgical resection and D2 lymph node (LN) dissection at a single tertiary care institution from 2010 to 2020 were analyzed. Patients with early stage (T1) tumors were assessed in detail to identify variables associated with regional LN metastasis including histologic differentiation, signet ring cells, demographics, smoking history, neoadjuvant therapy, and clinical staging by endoscopic ultrasound (EUS). We used standard statistical techniques including Mann-Whitney U and Chi-squared tests. RESULTS: Of 426 patients undergoing surgery for gastric cancer, 34% (n = 146) were diagnosed with T1 disease on surgical pathology. Among 146 T1 (T1a, T1b) gastric cancers, 24 patients [(17%) T1a (n = 4), T1b (n = 20)] had histologically confirmed regional LN metastases. The age at diagnosis ranged between 19 and 91 y and 54.8% were male. Prior smoking status was not associated with nodal positivity (P = 0.650). Of the 24 patients with positive LN on final pathology, seven patients received neoadjuvant chemotherapy. EUS was performed on 98 (67%) of the 146 T1 patients. Of these patients, 12 (13.2%) had positive LN on final pathology; however, none (0/12) were detected on preoperative EUS. There was no association between node status on EUS and node status on final pathology (P = 0.113). The sensitivity of EUS for N status was 0%, specificity was 84.4%, negative predictive value was 82.2% and positive predictive value was 0%. Signet ring cells were identified in 42% of node negative T1 tumors and 64% of node positive T1 tumors (P = 0.063). For LN positive cases on surgical pathology, 37.5% had poor differentiation, 42% had lymphovascular invasion, and regional nodal metastases were associated with increasing T stage (P = 0.003). CONCLUSIONS: T1 gastric cancer is associated with a substantial risk (17%) of regional LN metastasis, when pathologically staged following surgical resection and D2 lymphadenectomy. Clinically staged N+ disease by EUS was not significantly associated with pathologically staged N+ disease in these patients.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: Effects of postoperative fluids beyond the first 24 h.

BACKGROUND AND OBJECTIVES: There are no guidelines for intravenous fluid (IVF) administration after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). This study assessed rates of post-CRS/HIPEC morbidity according to perioperative IVF administration. METHODS: All patients undergoing CRS/HIPEC March 2007 to June 2018 were reviewed, recording clinicopathologic, operative, and postoperative variables. Patients were divided by peritoneal cancer index (PCI), comparing IVF volumes and types administered intraoperatively and during the first 72 h postoperatively. Optimal IVF rate cutoffs calculated using area under the receiver operating characteristic curves and Youden's index determined associations with complications. RESULTS: Overall, 185 patients underwent CRS/HIPEC, and 81 (51%) had low PCI (<10) and 77 (49%) had high PCI (≥10). In low-PCI patients, high IVF rates on postoperative days (POD) #0-2 were associated with higher overall complications: POD#0 (46% vs. 89%, p = 0.001), POD#1 (40% vs. 86%, p < 0.05), and POD#2 (42% vs. 72%, p < 0.05). High IVF rates were associated with respiratory distress (7% vs. 26%, p = 0.02) on POD#0, ileus (14% vs. 47%, p = 0.007) and intensive care unit stay (11% vs. 33%, p = 0.022) on POD#1, and ICU stay (8% vs. 33%, p = 0.003) on POD#2. CONCLUSIONS: For low PCI patients undergoing CRS/HIPEC, higher IVF rates were associated with postoperative complications. Post-CRS/HIPEC, IVF rates should be limited to prevent morbidity.

Perineural Invasion of Pancreatic Ductal Adenocarcinoma is Associated with Early Recurrence after Neoadjuvant Therapy Followed by Resection.

BACKGROUND: Neoadjuvant therapy (NAT) is increasingly utilized in the treatment of pancreatic ductal adenocarcinoma (PDAC). However, there are limited data on risk factors and patterns of recurrence after surgical resection. This study aimed to analyze timing and recurrence patterns of PDAC after NAT followed by curative resection. METHODS: The medical charts of patients with PDAC treated with NAT followed by curative-intent surgical resection at a single health system from January 1, 2012 to January 1, 2020 were retrospectively reviewed. Early recurrence was defined as recurrence within 12 months of surgical resection. RESULTS: 91 patients were included and median follow up was 20.1 months. Recurrence occurred in 50 (55%) patients, with median recurrence free survival (RFS) of 11.9 months. Overall, 18 (36%) patients had local and 32 (64%) had distant recurrences. Median RFS and overall survival (OS) between local and distant recurrence were similar. Perineural invasion (PNI) and the presence of a T2 + tumor was significantly higher in recurrence group than in no recurrence group. PNI was a significant risk factor for early recurrence. CONCLUSION: After NAT and surgical resection of PDAC, disease recurrence was common, with distant metastasis being the most common. PNI was significantly higher in the recurrence group.

Sarcopenia as a Predictor of Survival in Patients with Pancreatic Adenocarcinoma After Pancreatectomy.

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.

Gallbladder Cancer: A Single-Institution 10-Year Experience-Analysis of Adenocarcinoma Subtypes and Tumors Arising from Intracholecystic Papillary Neoplasms.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Neutrophil-to-Lymphocyte Ratio Predicts Recurrence Pattern in Patients with Resectable Colorectal Liver Metastases.

BACKGROUND: 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). METHODS: 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 (normal) or >3 (high). Recurrence risk was analysed using Fine and Gray correction for competing risk method and cause specific analyses. RESULTS: 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). CONCLUSIONS: 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.

Robotic-assisted Heller Myotomy Is a Safe Operation.

BACKGROUND: 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. OBJECTIVES: To describe our technique of performing robotic-assisted Heller myotomy and to review the initial results of this procedure. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Transanal endoscopic microsurgery under spinal anaesthesia.

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.

Paediatric community-acquired bacteraemia, pneumococcal invasive disease and antibiotic resistance fell after the pneumococcal conjugate vaccine was introduced.

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.

Excision of malignant and pre-malignant rectal lesions by transanal endoscopic microsurgery in patients under 50 years of age.

BACKGROUND: The most common technique for treating benign and early malignant rectal lesions is transanal endoscopic microsurgery (TEM). Local excision is an acceptable technique for high-risk and elderly patients, but there are hardly any data regarding young patients. AIM: To describe TEM outcomes in patients under 50 years of age. METHODS: We collected demographic, clinical, and pathological data from all patients under the age of 50 years who underwent the TEM procedure at Hasharon Rabin Medical Center from January 2005 to December 2018. RESULTS: During the study period, a total of 26 patients under the age of 50 years underwent TEM procedures. Their mean age was 43.3 years. Eleven (42.0%) were male. The mean operative time was 67 min, and the mean tumor size was 2.39 cm, with a mean anal verge distance of 8.50 cm. No major intraoperative or postoperative complications were recorded. The median length of stay was 2 d. Seven (26.9%) lesions were adenomas with low-grade dysplasia, four (15.4%) were high-grade dysplasia adenomas, two were T1 carcinomas (7.8%), and three were T2 carcinomas (11.5%). No residual disease was found following endoscopic polypectomy in two patients (7.8%), but four (15.4%) had other pathologies. Surgical margins were negative in all cases. Local recurrence was detected in one patient 33 mo following surgery. CONCLUSION: Among young adult patients, TEM for benign rectal lesions has excellent outcomes. It may also offer a balance between the efficacy of complete oncologic resection and postoperative quality of life in the treatment of rectal cancer. In some cases, it may be considered an alternative to radical surgery.

Actual and perceived gender differences in virtual tumor board participation.

Introduction: Participant characteristics are known to affect group discourse and discussion outcomes. In medicine, many decisions are made by group consensus, therefore an understanding of these factors is highly relevant. We aimed to measure the effects of participant characteristics on tumor board discussions. Methods: We performed a prospective, multi-institution, quantitative study of multi-disciplinary virtual tumor board meetings. Participant characteristics included age, gender, and clinical discipline. Outcomes of interest were speech events, duration, and discourse style. Participant impressions was assessed by a post-hoc survey. Results: A total of 361 cases were discussed across 32 virtual meetings. Of the 283 attendees, 66.4 % were women, and all moderators were men. Women comprised 43 % of the 54 speakers, thus speaking less than male attendees (p < 0.001). No significant differences were detected in the duration or style of speech between men and women. Women participants commented more frequently on cases where the clinical attending was a woman (4.09 comments by women vs. 2.99 comments by men, p < 0.001), and less frequently when the attending was a man (2.48 comments by women vs. 3.20 comments by men, p < 0.001). On post hoc survey, men responded that they introduced ideas, guided discussions, and succeeded in influencing decisions significantly more than women reported that they did. Conclusion: Women physicians were underrepresented in tumor boards as moderators, speakers, and attendings of record. Women physicians commented less on men physicians' patients. Women felt less impactful than their men counterparts, despite having the same duration and style of speech. Prompted participation, moderator feedback, talking points, and limiting the number of cases can be used to balance representation in discussions.

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.

Stage-specific regulation of Solanum lycopersicum leaf maturation by class 1 KNOTTED1-LIKE HOMEOBOX proteins.

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.

Surgical management of pancreatic cancer liver oligometastases.

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.

From organelle to organ: ZRIZI MATE-Type transporter is an organelle transporter that enhances organ initiation.

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.

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.