Incidence of clinically relevant postoperative pancreatic fistula in patients undergoing open and minimally invasive pancreatoduodenectomy: a population-based study.

Purpose: Postoperative pancreatic fistula (POPF) remains a devastating complication of pancreatoduodenectomy (PD). Minimally invasive PD (MIPD), including laparoscopic (LPD) and robotic (RPD) approaches, have comparable POPF rates to open PD (OPD). However, we hypothesize that the likelihood of having a more severe POPF, as defined as clinically relevant POPF (CR-POPF), would be higher in an MIPD relative to OPD. Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) targeted pancreatectomy dataset (2014-2020) was reviewed for any POPF after OPD. Propensity score matching (PSM) compared MIPD to OPD, and then RPD to LPD. Results: Among 3,083 patients who developed a POPF, 2,843 (92.2%) underwent OPD and 240 (7.8%) MIPD; of these, 25.0% were LPD (n = 60) and 75.0% RPD (n = 180). Grade B POPF was observed in 45.4% (n = 1,400), and grade C in 6.0% (n = 185). After PSM, MIPD patients had higher rates of CR-POPF (47.3% OPD vs. 54.4% MIPD, p = 0.037), as well as higher reoperation (9.1% vs. 15.3%, p = 0.006), delayed gastric emptying (29.2% vs. 35.8%, p = 0.041), and readmission rates (28.2% vs. 35.1%, p = 0.032). However, CR-POPF rates were comparable between LPD and RPD (56.8% vs. 49.3%, p = 0.408). Conclusion: The impact of POPF is more clinically pronounced after MIPD than OPD with a more complex postoperative course. The difference appears to be attributed to the minimally invasive environment itself as no difference was noted between LPD and RPD. A clear biological explanation of this clinical observation remains missing. Further studies are warranted.

Role of minimally invasive surgery in the management of localized pancreatic ductal adenocarcinoma: a review.

Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy with a minority of patients eligible for curative-intent surgical intervention. Pancreatic resections are technically demanding operations associated with considerable morbidity and mortality. Minimally invasive pancreatic resections (MIPRs), which include laparoscopic and robotic approaches, may enhance postoperative outcomes by lessening physiological impact of open surgery. A limited number of randomized-controlled trials as well as numerous retrospective reports have focused on MIPR outcomes and role in management of a variety of tumors, including PDAC. Today, MIPRs are generally considered acceptable alternatives to open surgery as a trend towards improved short-term metrics is observed. However, several questions remain regarding the oncological adequacy of MIPR's as long-term experience is less extensive compared to open techniques. This review aims to summarize existing evidence on MIPRs with a focus on PDAC.

Tamoxifen Response at Single-Cell Resolution in Estrogen Receptor-Positive Primary Human Breast Tumors.

PURPOSE: In estrogen receptor-positive (ER+)/HER2- breast cancer, multiple measures of intratumor heterogeneity are associated with a worse response to endocrine therapy. We sought to develop a novel experimental model to measure heterogeneity in response to tamoxifen treatment in primary breast tumors. EXPERIMENTAL DESIGN: To investigate heterogeneity in response to treatment, we developed an operating room-to-laboratory pipeline for the collection of live normal breast specimens and human tumors immediately after surgical resection for processing into single-cell workflows for experimentation and genomic analyses. Live primary cell suspensions were treated ex vivo with tamoxifen (10 µmol/L) or control media for 12 hours, and single-cell RNA libraries were generated using the 10X Genomics droplet-based kit. RESULTS: In total, we obtained and processed normal breast tissue from two women undergoing reduction mammoplasty and tumor tissue from 10 women with ER+/HER2- invasive breast carcinoma. We demonstrate differences in tamoxifen response by cell type and identify distinctly responsive and resistant subpopulations within the malignant cell compartment of human tumors. Tamoxifen resistance signatures from resistant subpopulations predict poor outcomes in two large cohorts of ER+ breast cancer patients and are enriched in endocrine therapy-resistant tumors. CONCLUSIONS: This novel ex vivo model system now provides the foundation to define responsive and resistant subpopulations within heterogeneous human tumors, which can be used to develop precise single cell-based predictors of response to therapy and to identify genes and pathways driving therapeutic resistance.

Tamoxifen Response at Single Cell Resolution in Estrogen Receptor-Positive Primary Human Breast Tumors.

In ER+/HER2- breast cancer, multiple measures of intra-tumor heterogeneity are associated with worse response to endocrine therapy. To investigate heterogeneity in response to treatment, we developed an operating room-to-laboratory pipeline for the collection of live human tumors and normal breast specimens immediately after surgical resection for processing into single-cell workflows for experimentation and genomic analyses. We demonstrate differences in tamoxifen response by cell type and identify distinctly responsive and resistant subpopulations within the malignant cell compartment of human tumors. Tamoxifen resistance signatures from 3 distinct resistant subpopulations are prognostic in large cohorts of ER+ breast cancer patients and enriched in endocrine therapy resistant tumors. This novel ex vivo model system now provides a foundation to define responsive and resistant sub-populations within heterogeneous tumors, to develop precise single cell-based predictors of response to therapy, and to identify genes and pathways driving resistance to therapy.

Dispensing and Purchasing Antibiotics Without Prescription: A Cross-sectional Study Among Pharmacists and Patients in Beirut, Lebanon.

Antimicrobial resistance is a global public health issue, exacerbated by dispensing and purchasing antibiotics without a prescription, common in low- and middle-income countries, such as Lebanon. This study aimed to (1) describe behavioral patterns underpinning dispensing and purchasing antibiotics without a prescription among pharmacists and patients, (2) describe reasons for, and (3) attitudes toward these behaviors. A cross-sectional study targeted pharmacists and patients, respectively, identified through stratified random sampling and convenience sampling from all 12 Beirut quarters. Questionnaires assessed behavioral patterns, reasons for, and attitudes toward dispensing and purchasing antibiotics without prescription among the 2 samples. A total of 70 pharmacists and 178 patients were recruited. About a third (37%) of pharmacists supported dispensing antibiotics without a prescription, considering it acceptable; 43% of patients report getting antibiotics without a prescription. Reasons for distributing and purchasing antibiotics without prescription include financial costs associated with the drugs and convenience, coupled with inexistent law enforcement. Dispensing antibiotics without prescription was shared among a relatively high proportion of pharmacists and patients residing in Beirut. Dispensing antibiotics without prescription is common in Lebanon, where law enforcement needs to be stronger. National efforts, including anti-AMR campaigns and law enforcement, must be rapidly implemented to avoid the double disease burden, especially when old and new vaccines are available, and superbugs are making preventative public health efforts more difficult.

High expression of the RET receptor tyrosine kinase and its ligand GDNF identifies a high-risk subset of estrogen receptor positive breast cancer.

PURPOSE: Resistance to endocrine therapy is the primary cause of treatment failure and death in patients with ER-positive (ER +)/luminal breast cancer. Expression and activation of the RET receptor tyrosine kinase may be driving poor outcomes. We aim to identify high-risk patients and druggable pathways for biomarker-based clinical trials. METHODS: We obtained batch-normalized mRNA expression data from Breast Invasive Carcinoma-The Cancer Genome Atlas, PanCancer Atlas (BRCA-TCGA). To determine clinically significant cutoffs for RET expression, patients were grouped at different thresholds for Kaplan-Meier plotting. Differential gene expression (DGE) analysis and enrichment for gene sets was performed. transcriptomic dataset of antiestrogen-treated ER + tumors stratified by clinical response was then analyzed. RESULTS: High RET expression was associated with worse outcomes in patients with ER + tumors, and stratification was enhanced by incorporating GDNF expression. High RET/GDNF patients had significantly lower overall survival (HR = 2.04, p = 0.012), progression-free survival (HR = 2.87, p < 0.001), disease-free survival (HR = 2.67, p < 0.001), and disease-specific survival (HR = 3.53, p < 0.001) than all other ER + patients. High RET/GDNF tumors were enriched for estrogen-independent signaling and targetable pathways including NTRK, PI3K, and KRAS. Tumors with adaptive resistance to endocrine therapy were enriched for gene expression signatures of high RET/GDNF primary tumors. CONCLUSION: Expression and activation of the RET receptor tyrosine kinase may be driving poor outcomes in some patients with ER + breast cancer. ER + patients above the 75th percentile may benefit from clinical trials with tyrosine kinase inhibitors.

Gas-Containing Biliary Calculi: Case Series and a Systematic Review.

BACKGROUND: Cholelithiasis is a common gallbladder finding leading to cholecystitis in 7% of cases. Sonographic imaging or computed tomography scans are commonly employed for the diagnosis of benign gallbladder disease. Air within the gallbladder might carry various diagnoses. As opposed to pathologic air in the gallbladder seen in emphysematous cholecystitis, gas-containing gallstones are no more pathological than the exclusive presence of gallstones. In the present report, we review the incidence, physiology, typical characteristics, and clinical significance of gas-containing gallstones within the gallbladder. METHODS: We performed an institutional review of all patients with benign gallbladder disease over the past 16 years (2005 to 2021) to identify patients with gas-containing gallstones in the gallbladder. We performed a review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) to identify all reported cases of patients with gas-containing biliary calculi within the gallbladder. RESULTS: Our institutional review identified 5 patients with gas-containing biliary calculi in 1252 consecutive cholecystectomies; 4 of which had cholecystitis, while 1 was an incidental finding. Our review of the literature identified 30 manuscripts documenting 54 unique patients with gas-containing biliary calculi. None of these patients had consequential pathology related to gas in the stones other than that caused by the gallstones (ie, biliary colic and cholecystitis). CONCLUSIONS: Gas-containing biliary calculi are uncommon. How gas finds itself within gallstones within the gallbladder is not entirely clear. Gas-containing gallstones should not be interpreted as free gas within the gallbladder or within an abscess.

The implications and management of complex biliary injuries at a tertiary hepatobiliary specialty center.

Injuries of the biliary tract and complex injuries involving vascular and parenchymal tissue can be detrimental despite the improved use of laparoscopy. Complex biliary injuries are variable depending on the type of injury as well as patient and surgeon factors. We present four cases of complex biliary injuries at our tertiary referral center with hepatobiliary expertise: biliary stenosis with obstruction, double duct system anatomy, combined right hepatic arterial transection and biliary duct injury, and a complete pedicle injury. Early identification and specialized repair of complex biliary injuries is essential to minimize patient morbidity. Notably, consulting a specialist intraoperatively in case of difficult dissection and visualization or a suspected injury and considering bail-out strategies such as a subtotal cholecystectomy or conversion are safe approaches to minimize complex biliary injuries. Earlier recognition and repair of complex biliary injuries improves outcomes when immediate intraoperative repair can be performed rather than delayed postoperatively.

Immunotherapy for metastatic liver disease from colorectal carcinoma: case series from the Middle East.

Immunotherapy poses new considerations and alterations to the management of metastatic colorectal carcinoma (mCRC), where chemotherapy achieves complete radiological response but yields complete pathological response in few patients only. Immunotherapy may be superior in the conversion of unresectable disease to resectable liver lesions from mCRC and downsizing borderline lesions for more feasible resectability and achieving complete pathologic response, with the potential for cure and to alter current, established guidelines for surgical resection with a shift from chemotherapy. We present two patients with hepatic lesions from mCRC characterized by deficient mismatch repair (dMMR) which were unresectable after traditional chemotherapy but were converted to resectable lesions with a complete histopathological response following immunotherapy. Complete histopathologic response and radiologic regression or disappearance of liver lesions was observed in patients with dMMR mCRC after pembrolizumab. Immunotherapy exhibits notable potential for cure, achieving complete, successful surgical resection and improving prognosis.

Metastatic melanoma to the small bowel causing intussusception: A case report.

INTRODUCTION AND IMPORTANCE: Melanoma is a malignant skin neoplasm with a high metastatic potential. Several reports have shown that metastatic melanoma has a predilection to metastasize to the GI tract; however, diagnosing metastatic melanoma as a cause of intussusception has been reported in only few cases with variable presentations. CASE PRESENTATION: We present the case of a 48-year-old woman with a long history of metastatic melanoma who presented with recurrent enteric intussusception due to a melanoma lesion acting as a pathologic lead point despite immunotherapy treatment. We contribute the management plan, diagnostic modalities, and surgical approach of this rare form of adult intussusception in guidance of future management plans. CLINICAL DISCUSSION: The variability in presentation of adult intussusception makes diagnosis difficult and the lack of consensus on management and surgical strategies poses challenging hurdles. A diagnostic laparoscopy followed by reduction and resection of the intussuscepted lesion in a small surgical field is an effective and beneficial palliative procedure with favorable outcomes. Our patient developed intussusception despite receiving a trial of dual immunotherapy after chemotherapy. CONCLUSION: It may be insufficient to control disease even with dual immunotherapy after chemotherapy. Further studies are needed to determine the optimal surgical and oncological management in treating gastrointestinal metastasis of malignant melanoma.

PTEN R130Q Papillary Tumor of the Pineal Region (PTPR) with Chromosome 10 Loss Successfully Treated with Everolimus: A Case Report.

Papillary tumors of the pineal region (PTPR) can be observed among adults with poor prognosis and high recurrence rates. Standards of therapy involve total surgical excision along with radiation therapy, with no promising prospects for primary adjuvant chemotherapy, as long-term treatment options have not been explored. Chromosome 10 loss is characteristic of PTPR, and PTEN gene alterations are frequently encountered in a wide range of human cancers and may be treated with mTORC1 inhibitors such as everolimus. In parallel, there are no reports of treating PTPR with everolimus alone as a monopharmacotherapy. We report the case of a patient diagnosed with PTPR (grade III) characterized by a PTEN R130Q alteration with chromosome 10 loss that was treated with everolimus pharmacotherapy alone, resulting in an asymptomatic course and tumor regression, a rare yet notable phenomenon not described in the literature so far with potential to alter the management approach to patients with PTPR.

Fertility in Breast Cancer Survivors in the Middle East: A Retrospective Study.

INTRODUCTION: By the time they complete breast cancer therapy, many young patients are still of childbearing age. We aim to estimate the incidence of pregnancies in women who completed treatment and examine the percentage of patients who received fertility counseling before initiation of therapy. MATERIAL AND METHODS: Electronic health records of breast cancer patients between 2008 and 2014 at AUBMC were screened for exclusion criteria of having metastatic disease or known infertility, still receiving therapy, and being above 42 years at diagnosis. Data about therapy and tumor characteristics was obtained for the included survivors who were interviewed as well via telephone for information about fertility preservation counseling, pregnancy occurrence, and delivery. RESULTS: 451 breast cancer patients were identified. 39 patients remained after application of exclusion criteria. 30.76% (n = 12) wanted more children at the time of diagnosis. 10.25% (n = 4) of all 39 patients treated for breast cancer achieved one or more pregnancy after a median time of 3.83 years after completion of therapy. 25% (n = 3) of women who wanted more children at diagnosis (n = 12) were able to conceive. 23.07% (n = 9) of patients discussed fertility with their primary oncologist prior to treatment initiation. 35.89% (n = 14) of patients were aware of fertility preservation technique availability, but none of these patients used one. CONCLUSIONS: The observed rate of pregnancy is comparable to the literature. There is a lack in fertility counseling of breast cancer patients, and the rate of use of fertility preservation techniques is very low despite prior knowledge about their availability.