Pancreaticoduodenectomy in the Middle East: Achieving optimal results through specialization and standardization.

BACKGROUND: Pancreaticoduodenectomy is a challenging surgical intervention that remains the cornerstone in the treatment of localized peri­ampullary pathologies. The concept of treatment standardization has been well-established in many high-volume centers in the world. Here, we present our experience in pancreaticoduodenectomy from 1994 to 2015. METHODS: We performed a retrospective review of the medical charts of patients who underwent pancreaticoduodenectomy at our institution. Data was entered to SPSS statistical software and analyzed. The Mann-Whitney U and Fisher's exact tests were used to report statistical differences between groups. RESULTS: Of the 370 patients who underwent pacreaticoduodenectomy, 300 were analyzed. The 1-, 3-, 5- and 10-year survival rates were 85%, 35%, 15%, and 7%, respectively with a 30-day mortality rate of 5.0% (15 patients). The median age of the patients was 61 (13-84) years, with 193 (64.3%) males and 107 (35.7%) females. The median operative time was 300 (130-570) min. The median postoperative length of hospital stay was 12 (5-76) days. Thirty-two patients required re-laparotomies; 10 for pancreatic leak, 7 for biliary leak and 15 for control of bleeding. Seventy-five (25.0%) patients developed pancreatic fistulae. Delayed gastric emptying was present in 31 (10.3%) patients. A significant improvement in surgical outcome was observed in cases done after 2008 which indicates the important role of specialized team in surgical management. CONCLUSIONS: The number of patients undergoing pancreaticoduodenectomy has been increasing annually over the past twenty-two years in our institution with results comparable to published series from high-volume centers. Through standardization of surgical techniques and perioperative management carried out by a specialist team, our results continue to improve despite the increasing complexity of cases referred to our unit.

Life Threatening Complications Post-Liposuction.

BACKGROUND: Liposuction is one of the most commonly performed aesthetic procedures. It is performed worldwide as an outpatient procedure. However, the complications are underestimated and underreported by caregivers. We present a case of delayed diagnosis of bilothorax secondary to liver and gallbladder injury after tumescent liposuction. METHODS: A 26-year-old female patient was transferred to our emergency department from an aesthetic clinic with worsening dyspnea, tachypnea and fatigue. She had undergone extensive liposuction of the thighs, buttocks, back and abdomen 5 days prior to presentation. RESULTS: A chest X-ray showed significant right-sided pleural effusion. Thoracentesis was performed and drained bilious fluid. CT scan of the abdomen revealed pleural, liver and gall bladder injury. An exploratory laparoscopy confirmed the findings, the collections were drained; cholecystectomy and intraoperative cholangiogram were performed. The patient did very well postoperatively and was discharged home in 2 days. CONCLUSION: Even though liposuction is considered a simple office-based procedure, its complications can be fatal. The lack of strict laws that exclusively place this procedure in the hands of medical professionals allow these procedures to still be done by less experienced hands and in outpatient-based settings. Our case serves to highlight yet another unique but potentially fatal complication of liposuction. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Chronic inflammatory demyelinating polyneuropathy caused by hepatocellular carcinoma.

Paraneoplastic syndromes are rare abnormal endocrine or immune responses triggered by neoplasms. Chronic inflammatory demyelinating polyneuropathy (CIDP) is one such example. CIDP is an acquired, immune-mediated neuropathy affecting the peripheral nerves and nerve roots. It is associated with many types of cancers, especially haematological malignancies. We report the case of a man in his 60s who presented to the emergency department with acute symptoms of upper and lower extremity paresis and decreased sensation in the toes and tips of his fingers. Laboratory tests were normal. Electrodiagnostic studies showed diffuse motor and sensory dysfunction in all extremities; a diagnosis of CIDP was consequently made. Imaging studies showed a large left lobe liver mass. Subsequent biopsy revealed histopathological findings characteristic of hepatocellular carcinoma. After failure of medical treatment with intravenous immunoglobulin and corticosteroids, laparoscopic resection of the tumour was planned, performed and resulted in complete resolution of symptoms. At 18 months postoperatively, the patient was asymptomatic.

Biospecimen Repositories in Low- and Middle-Income Countries: Insights From an American University of Beirut and Memorial Sloan Kettering Collaboration.

PURPOSE: Biobanking helps source tissue and blood for studying cancer genomics. Access to biorepository resources in low- and middle-income countries is lacking. Memorial Sloan Kettering Cancer Center (MSK) and the American University of Beirut (AUB) established a joint tissue biorepository at AUB in Beirut, Lebanon. The undertaking encountered key challenges that were unanticipated. MATERIALS AND METHODS: Patients age 18 years or older were eligible for enrollment at AUB. After consent, biospecimens were obtained at the time of routine diagnostic and/or therapeutic interventions. Both normal and abnormal tissue and solid and/or liquid specimens were collected from varied body sites. Early on, declining consent was frequently observed, and this was highlighted for investigation to understand potential participants reasoning. RESULTS: Of 850 patients approached, 704 (70.8%) elected to consent and 293 (29.5%) declined participation. The number of declined consents led to an amendment permitting the documentation of reasons for same. Of 100 potential participants who declined to consent and to whom outreach was undertaken, 63% indicated lack of research awareness and 27% deferral to their primary physician or family member. A financial gain for AUB was cited as concern by 5%, cultural boundaries in 4%, and 1% expressed concern about confidentiality. Of the patients who elected to consent, 682 biospecimens were procured. CONCLUSION: The AUB-MSK biospecimen repository has provided a unique resource for interrogation. Patient participation rate was high, and analyses of those who elected not to consent (29%) provide important insights into educational need and the local and cultural awareness and norms.

Choledochal anomalies in adults: A 20-year single-center retrospective cohort experience in the Middle East.

BACKGROUND AND STUDY AIMS: Choledochal cysts are rare congenital cystic dilatations of the bile ducts that occur in fewer than 1% of individuals. The disease is common in East Asia, and most of the literature concerns those populations, but some data about Western populations have been published recently. Long-term reports about the disease in Middle Eastern populations, however, are currently lacking. We report a single-center 20-year experience in diagnosing and managing choledochal anomalies. PATIENTS AND METHODS: Participants were adult patients in whom choledochal cysts were diagnosed over a 20-year (2000-2019) period at a single tertiary academic care center. Clinical data, including radiologic imaging findings, were retrieved from the patients' medical records. To describe the baseline characteristics of the population, we calculated descriptive statistics. RESULTS: Choledochal anomalies were diagnosed in 19 adult patients, whose median age was 30 years (interquartile range [IQR], 23-67 years). Of the choledochal cysts 13 (68.4%) were classified as Todani type I, 4 (21.1%) as Todani type IV, and 3 (15.8%) as Todani type V (Caroli's disease). No patient had underlying chronic liver disease, and liver synthetic function was preserved in all. Eighteen patients (94.7%) underwent surgery: cyst excision with Roux-en-Y hepaticojejunostomy in 17 and liver transplantation in 1. All 18 survived surgery, and the median postoperative hospital stay was 11 days (IQR, 5-34 days). All 18 were alive 90 days after surgery, and the median follow-up period was 40 months (IQR, 12-140 months). Seven patients (36.8%) developed postoperative surgical complications; 2 patients required rehospitalization, and 1 required reoperation. CONCLUSION: This description of adults with choledochal cysts is the latest long-term report about this disease in the Middle East. In our 20-year experience, the disease characteristics in our patients were moderately consistent with those described previously.

Hydatid Disease of the Liver in the Middle East: A Single Center Experience.

Background: Human cystic echinococcosis (CE), most commonly caused by echinococcosis granulosis, is the most common presentation of hydatid disease of the liver and is considered endemic in the Middle East region. Patients and Methods: This study is a retrospective single-center analysis of all patients with hepatic hydatid disease presenting for surgical management from 2001 to 2019. Results: From 2001 to 2019, 100 patients (54 males, 46 females) were diagnosed with hydatid disease of the liver with a mean age of 45 years (range, 19-82). The most common presenting symptom was right upper quadrant abdominal pain followed by incidental finding of cyst on imaging. Thirteen patients (13%) presented with signs and symptoms of obstructive jaundice. Of the 100 patients, 39 underwent laparoscopic surgery and 61 underwent open surgery. The most common complications were as follows: 16 bile leaks (16%), 14 intra-abdominal fluid collections (14%), 8 wound infections (8%), and 3 patients had biliary strictures (3%). Of the 100, 8 patients(8%) had recurrence of their hepatic hydatid disease. Conclusions: Hydatid disease of the liver is not a common disease, and its management can include medical, surgical, and interventional radiology. The decision depends on the size and complexity of the cyst and its location. Bile leak is a common complication and should be managed conservatively or through intervention by radiology or endoscopic retrograde cholangiopancreatography (ERCP).

Thymoquinone Radiosensitizes Human Colorectal Cancer Cells in 2D and 3D Culture Models.

Resistance of cancer cells and normal tissue toxicity of ionizing radiation (IR) are known to limit the success of radiotherapy. There is growing interest in using IR with natural compounds to sensitize cancer cells and spare healthy tissues. Thymoquinone (TQ) was shown to radiosensitize several cancers, yet no studies have investigated its radiosensitizing effects on colorectal cancer (CRC). Here, we combined TQ with IR and determined its effects in two-dimensional (2D) and three-dimensional (3D) culture models derived from HCT116 and HT29 CRC cells, and in patient-derived organoids (PDOs). TQ sensitized CRC cells to IR and reduced cell viability and clonogenic survival and was non-toxic to non-tumorigenic intestinal cells. TQ sensitizing effects were associated with G2/M arrest and DNA damage as well as changes in key signaling molecules involved in this process. Combining a low dose of TQ (3 µM) with IR (2 Gy) inhibited sphere formation by 100% at generation 5 and this was associated with inhibition of stemness and DNA repair. These doses also led to ~1.4- to ~3.4-fold decrease in organoid forming ability of PDOs. Our findings show that combining TQ and IR could be a promising therapeutic strategy for eradicating CRC cells.

Novel therapeutic diiminoquinone exhibits anticancer effects on human colorectal cancer cells in two-dimensional and three-dimensional in vitro models.

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality. Cancer stem cells (CSCs) in CRC, which are spared by many chemotherapeutics, have tumorigenic capacity and are believed to be the reason behind cancer relapse. So far, there have been no effective drugs to target colon CSCs. Diiminoquinone (DIQ) has shown promising effects on targeting colon cancer. However, there is limited research on the effects of DIQ on eradicating CSCs in CRC. AIM: To investigate the anticancer potential of DIQ on colon CSCs in two-dimensional (2D) and three-dimensional (3D) models using colonospheres and patient-derived organoids. METHODS: Various 2D methods have been used to assess the effect and the mechanism of DIQ on HCT116 and HT29 cell lines including cell proliferation and viability assays, migration and invasion assays, immunofluorescence staining, and flow cytometry. The potency of DIQ was also assessed in 3D culture using the sphere formation assay and colon cancer patient-derived organoid model. RESULTS: Our results showed that DIQ significantly inhibited cell proliferation, migration, and invasion in HCT116 and HT29 cell lines. DIQ treatment induced apoptosis along with an accumulation of HCT116 and HT29 cancer cells in the sub-G1 region and an increase in reactive oxygen species in both CRC cell lines. DIQ reduced sphere-forming and self-renewal ability of colon cancer HCT116 and HT29 stem/progenitor cells at sub-toxic doses of 1 µmol/L. Mechanistically, DIQ targets CSCs by downregulating the main components of stem cell-related -catenin, AKT, and ERK oncogenic signaling pathways. Potently, DIQ displayed a highly significant decrease in both the count and the size of the organoids derived from colon cancer patients as compared to control and 5-fluorouracil conditions. CONCLUSION: This study is the first documentation of the molecular mechanism of the novel anticancer therapeutic DIQ via targeting CSC, a promising compound that needs further investigation.

Robotic resection for hydatid disease of the liver.

Robotic-assisted surgery for the management of hepatic echinococcosis was introduced in 2016. The advantage it offers over laparoscopy is less rigidity with the use of the 360° rotation of the Endo-Wrist technology, thus allowing the preservation of the integrity of the liver tissue. Herein, we report the first successful robotic resection of the left lobe of the liver for hydatid disease in the Middle East. Our patient is a 71-year-old man found to have a large left hepatic lobe hydatid disease on CT scan. The hydatid liver disease was resected completely with an operation time of 130 min and minimal intraoperative blood loss. Patient did well postoperatively and was discharged home on day 2. Our experience shows that robotic surgery for hydatid disease of the liver can be safely performed, with an excellent outcome to the patient. It also provides unique technical advantages in the field of minimal-invasive surgery.

Prevalence of Insomnia among Pancreatic Cancer Patients following Pancreaticoduodenectomy.

INTRODUCTION: Sleep disturbances are more common in cancer patients than in the general population; however, there is limited research pertaining to the occurrence of such disturbances that subsequently impact patients' quality of life. The aim of our study is to describe the prevalence of insomnia among pancreatic cancer patients who have recently undergone recent pancreaticoduodenectomy. METHODS: We performed a 6-year (2014-2020) retrospective cohort analysis of all adult patients aged 18 and above with pancreatic cancer who underwent pancreaticoduodenectomy at our institution. Insomnia was characterized using the Pittsburgh Sleep Quality Index (PSQI). Symptoms of insomnia and the impact caused by these symptoms on daily lives were assessed with the Insomnia Severity Index (ISI), and patients were divided into mild insomnia (ISI 8-14) or moderate to severe insomnia (ISI ≥ 15). RESULTS: Out of forty patients with pancreatic cancer that have undergone pancreaticoduodenectomy, 19 (47.2%) reported that their sleep disturbances had a significant effect on their quality of life. A total of 22 (55.0%) patients reported insomnia, with 63.2% reporting mild insomnia. Chemotherapy was found to significantly increase the risk of moderate to severe insomnia. The mean ISI score was 7.2 ± 6.9, and the mean PSQI score was 7.0 ± 5.1. ISI and PSQI showed a strong positive correlation (r = 0.78, p < 0.01). CONCLUSION: Sleep disturbances such as insomnia following pancreatic cancer surgery are highly prevalent. Treating physicians and surgeons should recognize and routinely screen for sleep disorders through the management of a multidisciplinary team in order to alleviate some of the burden on the patients' mental well-being.

Spectrum of liver diseases in patients referred for Fibroscan: A single center experience in the Middle East.

BACKGROUND: Liver diseases is a worldwide etiology causing high morbidity and mortality. Fibroscan is a quick, painless examination performed in clinic or at the patient's bedside. It is used to evaluate liver status for patients with suspected liver disease prognosis. This study aims at describing the spectrum of liver diseases among patients performing Fibroscan at a tertiary care center in Lebanon. METHODS: This is a retrospective data collection study on patients who underwent Fibroscan at the American University of Beirut hepatobiliary unit between 2015 and 2018. Medical charts of all patients were reviewed. Data were collected and analyzed using SPSS 25 software. RESULTS: A total of 620 patients presented to the hepatobiliary unit for Fibroscan, of which 419 (67.5%) were males. The mean age was 47.8 ± 13.4 (range 18-84). 362(58.3%) had NAFLD, 89 (14.3%) had Hepatitis-B, 69 (11.1%) had Hepatitis-C, 48 (7.7%) had ALD, 20 (3.3%) had DILI, and 13 (2.9%) had autoimmune hepatitis. 190 (30.6%) were overweight (BMI over 25), 128 (20.6%) had diabetes. Liver stiffness corresponding to the diagnosis of F4 liver fibrosis stage on Fibroscan was mostly reported in 6 (46.5%) autoimmune hepatitis, 101 (27.9%) NAFLD, and 18 (26.1%) HCV patients. 141 (45.5%) patients who had one or more metabolic risk factors suffered from severe stage steatosis compared with 78 (28.9%) who had not any risk factors with P-value 0.04. CONCLUSIONS: Based on our sample, NAFLD is emerging as a predominant etiology of CLD, followed by, HBV, and HCV. This is the first study that reports CLD status in Lebanon, further studies that describe the prevalence and incidence of the disease at a larger scale are needed.

CYR61/CCN1 expression in resected pancreatic ductal adenocarcinoma: A retrospective pilot study of the interaction between the tumors and their surrounding microenvironment.

BACKGROUND: CCN1 is an extracellular matrix-associated protein thought to be implicated in tumor-stromal interaction in several solid tumors. The aim of our pilot study was to evaluate the correlation between CCN1 expression in stromal cells, pancreatic intraepithelial neoplasia (PanIN) and pancreatic ductal adenocarcinoma cells in resected pancreatic ductal adenocarcinoma (PDAC) specimens, and correlate that clinically. METHODS: A total of 42 paraffin-embedded PDAC tumor specimens were stained for CCN1 and evaluated via immunohistochemical (IHC) analysis. Statistical analysis was performed to correlate between CCN1 expression profiles in tumor tissues and clinicopathological parameters of patients. RESULTS: Our results showed CCN1 (CYR61) gene was highly expressed in PDAC tissues relative to other organ specific tumor tissues. Also, moderate and overexpression of CCN1 in PanIN was associated with PanIN grade 3 tissues. A statistically significant association was found between PanIN CCN1 scores on one hand and cancer stage, cancer grade, and CCN1 expression among ductal tumor cells and adjacent stromal cells on the other hand. DISCUSSION: The associations demonstrated suggest that CCN1 might be contributing to a substantial role in the interaction between the pancreatic tumors on one hand and their surrounding microenvironment and their precursors on the other hand; hence, it might serve as a potential therapeutic target for PDAC.

Gender differences in liver fibrosis among patients younger than 50 years: A retrospective cohort study.

BACKGROUND & AIMS: Liver fibrosis is a metabolic disease associated with several factors, mainly age, gender, immune suppression, viral hepatitis, alcohol and metabolic diseases. Here, we are assessing the gender impact on liver status in NAFLD patients younger than 50 years. METHODS: All males younger than 50 years and premenopausal females diagnosed with NAFLD were included in this study. Fibroscan results, demographics and clinical data were collected and analyzed by SPSS software. Patients were stratified based on fibrosis scores as mild or no fibrosis for F0-F1-F2 and severe fibrosis for F3 and F4. Data was analyzed and compared based on gender. RESULTS: A total of 221 patients 134 males and 80 premenopausal females were included. Factors that affected liver fibrosis scores were different between males and females, where only body-mass index (BMI), white blood cells (WBC) count, and glucose level were associated with severe liver fibrosis in females. Also, liver fibrosis scores were associated with severe liver fibrosis in males only, no difference in these scores was observed in premenopausal females with severe or mild liver fibrosis. CONCLUSIONS: Gender differences are prominent in NAFLD and different factors are associated with liver status in males as compared to females. Besides, fibrosis score could predict liver status in males but not in females. Further larger-scale studies are necessary to verify gender impact on liver fibrosis development.

Three different polymorphisms of the DPYD gene associated with severe toxicity following administration of 5-FU: a case report.

BACKGROUND: Dihydropyrimidine dehydrogenase deficiency secondary to polymorphisms in the DPYD gene can lead to significant toxicity associated with the administration of fluoropyrimidine chemotherapy. CASE PRESENTATION: We report a case of a 59-year-old Lebanese woman with metastatic pancreatic cancer who received FOLFIRINOX therapy and developed severe 5-fluorouracil toxicity after a single cycle. The entire DPYD gene was sequenced, and the patient was found to be heterozygous for three different polymorphisms that have reportedly been associated with dihydropyrimidine dehydrogenase deficiency. CONCLUSION: Because data regarding the prevalence and clinical significance of several heterozygous polymorphisms in a single DPYD gene are very limited, we suggest that full gene sequencing should be carried out, at least in populations in which the allele frequencies are unknown.

Perioperative Management of Pancreaticoduodenectomy: Avoiding Admission to the Intensive Care Unit.

INTRODUCTION: With the advancement in surgical expertise at high-volume centers and advances in perioperative management, pancreaticoduodenectomy is becoming safer and remains the gold standard for treating periampullary pathologies. We describe our experience in optimizing perioperative management in order to avoid admission to the intensive care unit and improve outcomes. METHOD: Retrospective data were collected on 370 surgical patients who underwent a pancreaticoduodenectomy between the years 1994 and 2016. RESULTS: Of the 370 patients, 200 operated between 2009 and 2016 did not require intensive care admission, blood transfusion, or central line insertion. The results were compared between different time intervals: before the year 1998, between the years 1998 and 2008, and between the years 2009 and 2016. The median blood loss dropped from 800 to 400 to 300 mL, respectively. The median operative time also dropped from 360 to 335 to 215 min, respectively. In addition, the median length of hospital stay decreased from 25 to 16 to 7 days, respectively. CONCLUSION: With the centralization of pancreaticoduodenectomy in high-volume centers and with specialized surgeons performing the surgery, there is a significant decrease in the onset of postoperative complications with a lesser need for blood transfusions and, subsequently, better recovery of patients without the need for intensive care unit admission.

Fibroscan and low-density lipoprotein as determinants of severe liver fibrosis in diabetic patients with nonalcoholic fatty liver disease.

BACKGROUND: Fibroscan is an effective and noninvasive tool to quantify fibrosis and steatosis in liver diseases including nonalcoholic fatty liver disease (NAFLD). Type-2-diabetes is a known risk factor for worse prognosis in NAFLD. In this study, we compare liver status in NAFDL diabetic and nondiabetic patients, identify potential risk factors, and determine the usefulness of Fibroscan in this population. PATIENTS AND METHODS: The charts of all patients with NAFLD who underwent Fibroscan at our institution were reviewed. Fibroscan results, demographics, and clinical data were collected and analyzed using SPSS software. RESULTS: Of the 248 NAFLD patients, 73 (29.4%) were diabetic and 175 (70.6%) were nondiabetic. As detected by the NAFLD' liver stiffness measure, 35 (47.94%) diabetic patients had severe liver fibrosis (F4) in contrast to only 46 (26.3%) nondiabetics. Diabetic patients also presented more with hypertension, dyslipidemia, coronary artery disease, and chronic kidney disease. Liver steatosis, liver function tests, and noninvasive scores did not vary significantly between the two groups, except for γ-glutamyltransferase, prothrombin time-international normalized ratio, and BMI-alanine aminotransferase ratio-diabetes score. Diabetic patients had significantly lower high-density lipoproteins and low-density lipoproteins. CONCLUSION: Fibroscan results and low-density lipoprotein are potential diagnostic factors of liver fibrosis in diabetic patients with NAFLD. Further studies are necessary to verify liver fibrosis diagnostic tools and prognostic and genetic markers in diabetic patients.

Erratum: Triple thrombophilic simultaneous mutations in patients after bariatric surgery: is there a role for screening in the Eastern Mediterranean?

[This corrects the article DOI: 10.1093/jscr/rjy135.][This corrects the article DOI: 10.1093/jscr/rjy135.].

Triple thrombophilic simultaneous mutations in patients after bariatric surgery: is there a role for screening in the Eastern Mediterranean?

BACKGROUND AND PURPOSE: Thrombophilia is a hypercoagulable state that predisposes to thrombosis. Several genetic risk factors have been shown to predispose to thromboembolic events. Homozygosity to a thrombophilic mutation certainly predisposes the affected patient to more serious symptoms. MATERIALS AND METHODS: Here we present a case of a 56-year-old male patient who underwent sleeve gastrectomy for morbid obesity, presenting to our institution with abdominal pain. Investigations revealed thrombosis of the splenic, axillary vein as well as the right pulmonary artery. The patient was found to have triple thrombophilic mutations. RESULTS: To our knowledge, this is the first reported case of three specific simultaneous thrombophilic mutations in a patient from the Eastern Middle East. CONCLUSION: We suggest a role for screening for thrombophilic mutations in the Eastern Mediterranean patients undergoing bariatric surgeries for morbid obesity due to the increased risk of thrombosis in this group of patients.