The Role of Hepatobiliary Scintigraphy as the Initial Investigative Modality for Significant Bile Leak following Laparoscopic Cholecystectomy.

INTRODUCTION: Currently, the rate of bile duct injury and leak following laparoscopic cholecystectomy (LC) is still higher than for open surgery. Diverse investigative algorithms were suggested for bile leak, shifting from hepatobiliary scintigraphy (HBS) toward invasive and more sophisticated means. We aimed to analyze the use of biliary scan as the initial modality to investigate significant bile leak in the drain following LC, attempting to avoid potential unnecessary invasive means when the scan demonstrate fair passage of nuclear substance to the intestine, without leak. METHODS: We have conducted a prospective non-randomized study, mandating hepatobiliary scintigraphy first, for asymptomatic patients harboring drain in the gallbladder fossa, leaking more than 50 mL/day following LC. Analysis was done based on medical data from the surgical, gastroenterology, and the nuclear medicine departments. RESULTS: Among 3,124 patients undergoing LC, significant bile leak in the drain was seen in 67 subjects, of whom we started with HBS in 50 patients, presenting our study group. In 27 of whom, biliary scan was the only investigative modality, showing fair passage of the nuclear isotope to the duodenum and absence of leak in the majority. The leak stopped spontaneously within a mean of 3.6 days, and convalescence as well as outpatient clinic follow-up was uneventful. In 23 patients, biliary scan that was interpreted as abnormal was followed by endoscopic retrograde cholangio-pancreatography (ERCP). However, ERCP did not demonstrate any bile leak in 13 subjects. In 17 patients, ERCP was used initially, without biliary scan, suggesting the possibility of avoiding invasive modalities in 7 patients. CONCLUSIONS: Based on a negative predictive value of 91%, we suggest that in cases of asymptomatic significant bile leak through a drain following LC, a normal HBS as the initial modality can safely decrease the rate of using invasive modalities.

Delayed diagnosis and subsequently increased severity of acute appendicitis (compatible with clinical-pathologic grounds) during the COVID-19 pandemic: an observational case-control study.

BACKGROUND: During a global crisis like the current COVID-19 pandemic, delayed admission to hospital in cases of emergent medical illness may lead to serious adverse consequences. We aimed to determine whether such delayed admission affected the severity of an inflammatory process regarding acute appendicitis, and its convalescence. METHODS: In a retrospective observational cohort case-control study, we analyzed the medical data of 60 patients who were emergently and consecutively admitted to our hospital due to acute appendicitis as established by clinical presentation and imaging modalities, during the period of the COVID-19 pandemic (our study group). We matched a statistically control group consisting of 97 patients who were admitted during a previous 12-month period for the same etiology. All underwent laparoscopic appendectomy. The main study parameters included intraoperative findings (validated by histopathology), duration of abdominal pain prior to admission, hospital stay and postoperative convalescence (reflecting the consequences of delay in diagnosis and surgery). RESULTS: The mean duration of abdominal pain until surgery was significantly longer in the study group. The rate of advanced appendicitis (suppurative and gangrenous appendicitis as well as peri-appendicular abscess) was greater in the study than in the control group (38.3 vs. 21.6%, 23.3 vs. 16.5%, and 5 vs. 1% respectively), as well as mean hospital stay. CONCLUSIONS: A global crisis like the current viral pandemic may significantly affect emergent admissions to hospital (as in case of acute appendicitis), leading to delayed surgical interventions and its consequences.

The volume of general surgery emergency cases in a government hospital during the COVID-19 pandemic and two other periods: a comparative, retrospective study.

BACKGROUND: During March and April 2020, reductions in non-COVID-19 hospital admissions were observed around the world. Elective surgeries, visits with general practitioners, and diagnoses of medical emergencies were consequently delayed. OBJECTIVE: To compare the characteristics of patients admitted to a northern Israeli hospital with common surgical complaints during three periods: the lockdown due to the COVID-19 outbreak, the Second Lebanon War in 2006, and a regular period. METHODS: Demographic, medical, laboratory, imaging, intraoperative, and pathological data were collected from electronic medical files of patients who received emergency treatment at the surgery department of a single hospital in northern Israel. We retrospectively compared the characteristics of patients who were admitted with various conditions during three periods. RESULTS: Patients' mean age and most of the clinical parameters assessed were similar between the periods. However, pain was reportedly higher during the COVID-19 than the control period (8.7 vs. 6.4 on a 10-point visual analog scale, P < 0.0001). During the COVID-19 outbreak, the Second Lebanon War, and the regular period, the mean numbers of patients admitted daily were 1.4, 4.4, and 3.0, respectively. The respective mean times from the onset of symptoms until admission were 3, 1, and 1.5 days, P < 0.001. The respective proportions of surgical interventions for appendiceal disease were 95%, 96%, and 69%; P = 0.03. CONCLUSIONS: Compared to a routine period, patients during the COVID-19 outbreak waited longer before turning to hospitalization, and reported more pain at arrival. Patients during both emergency periods were more often treated surgically than non-operatively.

A unusual case of multifocal pyogenic abscess formation following ERCP procedure.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is essential for managing biliary and pancreatic disorders. Infection is the most morbid complication of ERCP and among the most common causes of ERCP-related death. CASE PRESENTATION: A 69-year-old man presented with right upper quadrant abdominal pain, obstructive jaundice and abnormal liver function tests. Ultrasound revealed cholelithiasis without bile duct dilation. After receiving intravenous antibiotics for acute cholecystitis, the patient was discharged. Two weeks later, an endoscopic ultrasound demonstrated gallstones and CBD dilation of up to 6.4 mm with 2 filling defects. An ERCP was performed with a papillotomy and stone extraction. Twenty-four hours post-ERCP the patient developed a fever, chills, bilirubinemia and elevated liver function tests. Ascending cholangitis was empirically treated using Ceftriaxone and Metronidazole. However, the patient remained febrile, with a diffusely tender abdomen and elevated inflammatory markers. A CT revealed a very small hypodense lesion in the seventh liver segment. Extended-spectrum beta-lactamase positive Klebsiella Pneumonia and Enterococcus Hirae were identified, and the antibiotics were switched to Imipenem and Cilastatin. The hypodense lesion in the liver increased to 1.85 cm and a new hypodense lesion was seen in the right psoas. At day 10 post-ERCP, the patient started having low back pain and difficulty walking. MRI revealed L4-L5 discitis with a large epidural abscess, spanning L1-S1 and compressing the spinal cord. Decompressive laminectomy of L5 was done and Klebsiella pneumonia was identified. Due to continued drainage from the wound, high fever, we performed a total body CT which revealed increased liver and iliopsoas abscess. Decompressive laminectomy was expanded to include L2-L4 and multiple irrigations were done. Gentamycin and Vancomycin containing polymethylmethacrylate beads were implanted locally and drainage catheters were placed before wound closure. Multidisciplinary panel discussion was performed, and it was decided to continue with a non invasive approach . CONCLUSIONS: Early recognition of complications and individualized therapy by a multi-disciplined team is important for managing post-ERCP septic complications. Particular attention should be given to adequate coverage by empiric antibiotics.

Chylous ascites as a late complication of one anastomosis gastric bypass-minigastric bypass: case report.

BACKGROUND: One anastomosis gastric bypass- minigastric bypass (OAGB-MGB) is an emerging bariatric surgery that is being endorsed by surgeons worldwide. Internal herniation is a rare and dreaded complication after malabsorptive bariatric procedures, which necessitates early diagnosis and intervention. CASE PRESENTATION: We describe a 29-year-old male with chylous ascites caused by an internal hernia 8 months following laparoscopic one anastomosis gastric bypass. An abdominal CT showed enlargement of lymph nodes at the mesentery, with a moderate amount of liquid in the abdomen and pelvis. An emergent exploratory laparoscopic surgery demonstrated an internal hernia at the Petersen's space with a moderate quantity of chylous ascites. The patient made an uneventful recovery after surgery. CONCLUSIONS: Internal herniation can occur after OAGB-MGB and in extremely rare cases lead to chylous ascites. To our knowledge, this is the first reported case of chylous ascites following one anastomosis gastric bypass.

Increased Intra-abdominal Pressure Induces Acute Kidney Injury in an Experimental Model of Congestive Heart Failure.

BACKGROUND: Congestive heart failure (CHF) entails a complex interaction between the heart and the kidney that represents a clinical entity called cardiorenal syndrome (CRS). One of the mechanisms underlying CRS includes increased intra-abdominal pressure (IAP). We examined the effect of elevated IAP on kidney function in rats with low- and high-output CHF. METHODS AND RESULTS: Rats with compensated and decompensated CHF induced by means of aortocaval fistula, rats with myocardial infraction (MI) induced by means of left anterior descending artery ligation, and sham control rats were subjected to either 10 or 14 mm Hg IAP. Urine flow (V), Na+ excretion (UNaV), glomerular filtration rate (GFR), and renal plasma flow (RPF) were determined. The effects of pretreatment with tadalafil (10 mg/kg orally for 4 days) on the adverse renal effects of IAP were examined in decompensated CHF and MI. Basal V and GFR were significantly lower in rats with decompensated CHF compared with sham control rats. Decompensated CHF rats and MI rats subjected to 10 and 14 mm Hg IAP exhibited more significant declines in V, UNaV, GFR and RPF than compensated and sham controls. Elevated IAP also induced tubular injury, as evidenced by significantly increased absolute urinary excretion of neutrophil gelatinase-associated lipocalin. In addition, in a nonquantitative histologic analysis, elevated IAP was associated with increase in necrosis and cell shedding to the tubule lumens, especially in the decompensated CHF subgroup. Pretreatment of decompensated CHF rats and MI rats with tadalafil ameliorated the adverse renal effects of high IAP. CONCLUSIONS: Elevated IAP contributes to kidney dysfunction in high- and low-cardiac output CHF. IAP induces both hemodynamic alterations and renal tubular dysfunction. These deleterious effects are potentially reversible and can be ameliorated with the use of phosphodiesterase-5 inhibition.

Correction to: The mTOR inhibitor rapamycin down-regulates the expression of the ubiquitin ligase subunit Skp2 in breast cancer cells.

After the publication of this work [1], an error was noticed in Fig. 2b, Fig. 3a and Fig. 5b. The Skp1 loading control was accidentally duplicated. We apologize for this error, which did not affect any of the interpretations or conclusions of the article.

International consensus guidelines on robotic pancreatic surgery in 2023.

Background: With the rapid development of robotic surgery, especially for the abdominal surgery, robotic pancreatic surgery (RPS) has been applied increasingly around the world. However, evidence-based guidelines regarding its application, safety, and efficacy are still lacking. To harvest robust evidence and comprehensive clinical practice, this study aims to develop international guidelines on the use of RPS. Methods: World Health Organization (WHO) Handbook for Guideline Development, GRADE Grid method, Delphi vote, and the AGREE-II instrument were used to establish the Guideline Steering Group, Guideline Development Group, and Guideline Secretary Group, formulate 19 clinical questions, develop the recommendations, and draft the guidelines. Three online meetings were held on 04/12/2020, 30/11/2021, and 25/01/2022 to vote on the recommendations and get advice and suggestions from all involved experts. All the experts focusing on minimally invasive surgery from America, Europe and Oceania made great contributions to this consensus guideline. Results: After a systematic literature review 176 studies were included, 19 questions were addressed and 14 recommendations were developed through the expert assessment and comprehensive judgment of the quality and credibility of the evidence. Conclusions: The international RPS guidelines can guide current practice for surgeons, patients, medical societies, hospital administrators, and related social communities. Further randomized trials are required to determine the added value of RPS as compared to open and laparoscopic surgery.

Mixed neuroendocrine tumor of the common bile duct.

CONTEXT: Mixed adenoendocrine tumors of the extrahepatic bile ducts are exceedingly rare and most of those who are rarely diagnosed are adenocarcinomas. Neuroendorine tumors accounts for only 0.2-2%. CASE REPORT: We report a case of mixed adenoneuroendo-carcinoma of the common bile duct in an 82-year-old male. CONCLUSION: Clinical experience suggests that the neuroendocrine component of mixed tumors behave more aggressively than the regular biliary adenocarcinoma component. This clinical behavior may have an important role in the management of this clinical entity.

The epidermal growth factor receptor mediates tumor necrosis factor-alpha-induced activation of the ERK/GEF-H1/RhoA pathway in tubular epithelium.

Tumor necrosis factor (TNF)-α induces cytoskeleton and intercellular junction remodeling in tubular epithelial cells; the underlying mechanisms, however, are incompletely explored. We have previously shown that ERK-mediated stimulation of the RhoA GDP/GTP exchange factor GEF-H1/Lfc is critical for TNF-α-induced RhoA stimulation. Here we investigated the upstream mechanisms of ERK/GEF-H1 activation. Surprisingly, TNF-α-induced ERK and RhoA stimulation in tubular cells were prevented by epidermal growth factor receptor (EGFR) inhibition or silencing. TNF-α also enhanced phosphorylation of the EGFR. EGF treatment mimicked the effects of TNF-α, as it elicited potent, ERK-dependent GEF-H1 and RhoA activation. Moreover, EGF-induced RhoA activation was prevented by GEF-H1 silencing, indicating that GEF-H1 is a key downstream effector of the EGFR. The TNF-α-elicited EGFR, ERK, and RhoA stimulation were mediated by the TNF-α convertase enzyme (TACE) that can release EGFR ligands. Further, EGFR transactivation also required the tyrosine kinase Src, as Src inhibition prevented TNF-α-induced activation of the EGFR/ERK/GEF-H1/RhoA pathway. Importantly, a bromodeoxyuridine (BrdU) incorporation assay and electric cell substrate impedance-sensing (ECIS) measurements revealed that TNF-α stimulated cell growth in an EGFR-dependent manner. In contrast, TNF-α-induced NFκB activation was not prevented by EGFR or Src inhibition, suggesting that TNF-α exerts both EGFR-dependent and -independent effects. In summary, in the present study we show that the TNF-α-induced activation of the ERK/GEF-H1/RhoA pathway in tubular cells is mediated through Src- and TACE-dependent EGFR activation. Such a mechanism could couple inflammatory and proliferative stimuli and, thus, may play a key role in the regulation of wound healing and fibrogenesis.

Hypervascular lesion in the head of the pancreas. Preoperative angiography and selective embolization results in bloodless operation.

CONTEXT: Pancreatic neuroendocrine tumors (PNETs) are rare tumors. These tumors are hypervascular in nature. Their surgical management is well described and practiced. Although hypervascular in their nature, preoperative angioembolization of the primary tumor is usually not indicated. CASE REPORT: We describe a case of an extremely hypervascular PNET in the head of the pancreas that was managed with preoperative angioembolization that was followed by a Whipple operation that resulted in excellent recovery. DISCUSSION: Pre-operative angioembolization of pancreatic tumors, although previously reported, is exceedingly rare. The use of this technique prior to surgery is feasible and may result in bloodless surgery and better outcome.

Resection of an axillary macrocystic lymphatic malformation in a 14-year-old girl using intraoperative indocyanine green lymphography.

Lymphangioma is a malformation of the lymphatic system for which surgical excision is a possible treatment. However, complete excision may be hindered by the lesion's size, anatomic location, unclear borders, and invasion into adjacent tissues. We describe a 14-year-old girl who presented with a rapidly progressing axillary swelling. Magnetic resonance imaging and ultrasound revealed a lymphatic macrocystic multilocular lesion. After preoperative and intraoperative indocyanine green lymphography, a complete surgical excision was achieved without damage to collateral lymphatic channels or surrounding tissues. Intraoperative indocyanine green lymphography may be useful in achieving efficient and safe resection of lymphangioma without damaging unconnected lymphatics.

Emergency open surgery with a duodenotomy and successful removal of an impacted basket following a complicated endoscopic retrograde cholangiopancreatography procedure: a case report.

BACKGROUND: Current management of choledocholithiasis entails the use of endoscopic retrograde cholangiopancreatography (ERCP) and clearance of the common bile duct. A rare complication of this procedure is the impaction of the basket by a large stone, which necessitates lithotripsy. Here we report a case of an impacted basket during ERCP, which was managed by open surgery with a duodenotomy and the manual removal of the basket. CASE PRESENTATION: A 79-year-old Caucasian man was admitted to our department with yellowish discoloration of urine, skin and eyes. Abdominal ultrasonography showed a slightly thickened gallbladder, multiple gallbladder stones, dilated intrahepatic bile ducts and extrahepatic bile extending to 1.1 cm. A computed tomography (CT) scan demonstrated a stone in the common bile duct, which caused dilation of the biliary ducts. The patient was diagnosed with obstructive jaundice secondary to choledocholithiasis; and underwent an ERCP, a sphincterotomy and stone extraction. Four days following discharge, the patient was readmitted with jaundice, abdominal pain, vomiting and fever. He was diagnosed with ascending cholangitis and treated initially with antibiotics. A second ERCP revealed a dilated common bile duct and choledocholithiasis. Stone removal with a basket failed, as did mechanical lithotripsy. Finally, the wires of the basket were ruptured and stacked in the common bile duct together with the stone. During exploratory laparotomy, adhesiolysis, a Kocher maneuver of the duodenum and a subtotal cholecystectomy were performed. Choledochotomy did not succeed in removing the impacted wires together with the stone. Therefore, a duodenotomy and an extension of the sphincterotomy were performed, followed by high-pressure lavage of the common bile duct to remove additional small biliary stones. The choledochotomy and duodenotomy were closed by a one-layer suture, and a prophylactic gastroenterostomy was performed to prevent leakage from the common bile duct and the duodenum. The postoperative course was satisfactory. CONCLUSIONS: This is the first report in the literature of removal of an impacted Dormia basket through the papilla by performing a duodenotomy and an extension of the sphincterotomy, followed by gastroenterostomy.

Microsurgery for management of primary and secondary lymphedema.

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of lymphaticovenular anastomosis (LVA) in patients with lymphedema. METHODS: A retrospective analysis was conducted of 70 patients suffering from primary or secondary lymphedema who underwent LVA surgery with indocyanine green fluorescence lymphangiography. Postoperative evaluation included qualitative and quantitative volumetric assessment and analysis. Limb volume was measured by circumferential tape measurement volumetric method, in which the limb is subdivided into five segments and each segment's circumference is measured. RESULTS: LVA was performed in 70 patients, 22 with primary lymphedema and 48 with secondary lymphedema. The difference in preoperative upper limb volume was 35% with mean postoperative follow-up of 9 months. The mean number of lymphovenous bypasses was 3.9. The reduction in limb volume at 3, 6, and 12 months was 40.4%, 41%, and 45%, respectively. Patients with early-stage lymphedema had significantly higher volume reductions than patients with late-stage lymphedema at 3, 6, and 12 months (48% vs 18%, 49% vs 22%, and 65% vs 31%; P < .001). For lower extremity lymphedema, the preoperative volume differential was 25.5%. The mean postoperative follow-up was 9 months. The reduction in limb volume at 3, 6, and 12 months was 28%, 37%, and 39%, respectively. CONCLUSIONS: LVA surgery is a safe and effective method of reducing lymphedema severity, especially in upper extremity lymphedema at an earlier disease stage.

Robotic inguinal hernia repair: Is it a new era in the management of inguinal hernia?

OBJECTIVE: We compared outcomes of elective inguinal hernia repair performed at one institution by three approaches: robotic-assistance, laparoscopic, and open. METHODS: Characteristics of the patients, the hernia and the procedures performed during 2014-2016 were accessed from patient electronic medical files of 137 elective inguinal hernia repairs. 24 surgeries were robotic-assisted, 16 laparoscopic and 97 open repairs. RESULTS: Distributions of age, sex and BMI did not differ between the groups. Bilateral repair was more common in the robotic (70.8%) than the laparoscopic (50.0%) and open groups (12.4%) (p < 0.001). Direct hernias were more common in the open (45.4%) than the robotic (20.8%) and laparoscopic (12.5%) groups (p < 0.001). Only 3 hernias were inguinoscrotal, all in the robotic group. The median operation times were 44.0, 79.0 and 92.5 min for the open, laparoscopic and robotic methods, respectively (p < 0.001). Among the unilateral repairs, the median operative times were the same for the robotic and laparoscopic procedures, 73 min, and less for the open procedures, 40 min. The proportion of patients hospitalized for 2-3 days was higher for open repair (13.4% vs. 6.2% and 0% for laparoscopic and robotic), but this difference was not statistically significant. The median maximal postoperative pain according to a 0-10-point visual analogue score was 5.0, 2.0 and 0 for open, laparoscopic and robotic procedures, respectively (p < 0.001). CONCLUSIONS: This report demonstrated the safety and feasibility of robotic-assisted inguinal hernia repair.

International consensus statement on robotic pancreatic surgery.

The robotic surgical system has been applied to various types of pancreatic surgery. However, controversies exist regarding a variety of factors including the safety, feasibility, efficacy, and cost-effectiveness of robotic surgery. This study aimed to evaluate the current status of robotic pancreatic surgery and put forth experts' consensus and recommendations to promote its development. Based on the WHO Handbook for Guideline Development, a Consensus Steering Group* and a Consensus Development Group were established to determine the topics, prepare evidence-based documents, and generate recommendations. The GRADE Grid method and Delphi vote were used to formulate the recommendations. A total of 19 topics were analyzed. The first 16 recommendations were generated by GRADE using an evidence-based method (EBM) and focused on the safety, feasibility, indication, techniques, certification of the robotic surgeon, and cost-effectiveness of robotic pancreatic surgery. The remaining three recommendations were based on literature review and expert panel opinion due to insufficient EBM results. Since the current amount of evidence was low/meager as evaluated by the GRADE method, further randomized controlled trials (RCTs) are needed in the future to validate these recommendations.

The mTOR inhibitor rapamycin down-regulates the expression of the ubiquitin ligase subunit Skp2 in breast cancer cells.

INTRODUCTION: Loss of the cyclin-dependent kinase inhibitor p27 is associated with poor prognosis in breast cancer. The decrease in p27 levels is mainly the result of enhanced proteasome-dependent degradation mediated by its specific ubiquitin ligase subunit S phase kinase protein 2 (Skp2). The mammalian target of rapamycin (mTOR) is a downstream mediator in the phosphoinositol 3' kinase (PI3K)/Akt pathway that down-regulates p27 levels in breast cancer. Rapamycin was found to stabilize p27 levels in breast cancer, but whether this effect is mediated through changes in Skp2 expression is unknown. METHODS: The expression of Skp2 mRNA and protein levels were examined in rapamycin-treated breast cancer cell lines. The effect of rapamycin on the degradation rate of Skp2 expression was examined in cycloheximide-treated cells and in relationship to the anaphase promoting complex/Cdh1 (APC\C) inhibitor Emi1. RESULTS: Rapamycin significantly decreased Skp2 mRNA and protein levels in a dose and time-dependent fashion, depending on the sensitivity of the cell line to rapamycin. The decrease in Skp2 levels in the different cell lines was followed by cell growth arrest at G1. In addition, rapamycin enhanced the degradation rate of Skp2 and down-regulated the expression of the APC\C inhibitor Emi1. CONCLUSION: These results suggest that Skp2, an important oncogene in the development and progression of breast cancer, may be a novel target for rapamycin treatment.

International consensus statement on robotic pancreatic surgery

The robotic surgical system has been applied to various types of pancreatic surgery. However, controversies exist regarding a variety of factors including the safety, feasibility, efficacy, and cost-effectiveness of robotic surgery. This study aimed to evaluate the current status of robotic pancreatic surgery and put forth experts' consensus and recommendations to promote its development. Based on the WHO Handbook for Guideline Development, a Consensus Steering Group* and a Consensus Development Group were established to determine the topics, prepare evidence-based documents, and generate recommendations. The GRADE Grid method and Delphi vote were used to formulate the recommendations. A total of 19 topics were analyzed. The first 16 recommendations were generated by GRADE using an evidence-based method (EBM) and focused on the safety, feasibility, indication, techniques, certification of the robotic surgeon, and cost-effectiveness of robotic pancreatic surgery. The remaining three recommendations were based on literature review and expert panel opinion due to insufficient EBM results. Since the current amount of evidence was low/meager as evaluated by the GRADE method, further randomized controlled trials (RCTs) are needed in the future to validate these recommendations.

Cecal fibromatosis (desmoid tumor) mimicking periappendicular abscess: a case report.

A 32-year-old man presented to our department with abdominal pain and fever. In an earlier hospitalization he was diagnosed with periappendicular abscess and treated with antibiotics. Due to fever and 'non-resolution' of the abscess and due to its deep location in the lower abdomen, which excluded percutaneous drainage, we elected to operate the patient. A large mass in the cecum accompanied with an abscess resulted in a right hemicolectomy. The pathological examination revealed a desmoid tumor of the cecum. The patient's recovery was uneventful.