M. Usman Ahmad

All Publications

• Distal Pancreatectomy with and without Celiac Axis Resection for Adenocarcinoma: A Comparison in the Era of Neoadjuvant Therapy. Cancers Daniel, S. K., Hironaka, C. E., Ahmad, M. U., Delitto, D., Dua, M. M., Lee, B., Norton, J. A., Visser, B. C., Poultsides, G. A. 2024; 16 (20)

  Abstract

  Distal pancreatectomy with celiac axis resection (DP-CAR) has been used for selected patients with pancreatic cancer infiltrating the celiac axis. We compared the short- and long-term outcomes between DP-CAR and distal pancreatectomy alone (DP) in patients receiving neoadjuvant therapy.Patients undergoing DP-CAR from 2013 to 2022 were retrospectively reviewed. Clinicopathologic features, post-operative morbidity, and survival outcomes were compared with patients undergoing DP after neoadjuvant chemotherapy.Twenty-two DP-CAR and thirty-four DP patients who underwent neoadjuvant chemotherapy were identified. There were no differences in comorbidities or CA19-9 levels. OR time was longer for DP-CAR (304 vs. 240 min, p = 0.007), but there was no difference in the transfusion rate (22.7% vs. 14.7%). Vascular reconstruction was more common in DP-CAR (18.2% vs. 0% arterial, p = 0.05; 40.9% vs. 12.5% venous, p = 0.04). There was no difference in morbidity or mortality between the two groups. Although there was a trend towards larger tumors in DP-CAR (5.1 cm vs. 3.8 cm, p = 0.057), the overall survival from the initiation of treatment (32 vs. 28 months, p = 0.43) and surgery (30 vs. 24 months, p = 0.43) were similar.DP-CAR is associated with similar survival and morbidity compared to DP patients requiring neoadjuvant chemotherapy and should be pursued in appropriately selected patients.

  View details for DOI 10.3390/cancers16203467

  View details for PubMedID 39456561

• Review of Role of Surgery with Electroporation in Melanoma: Chemotherapy, Immunotherapy, and Gene Delivery. Journal of clinical medicine Ahmad, M. U., Walsh, A., Kirane, A. 2024; 13 (13)

  Abstract

  Electroporation with chemotherapy (ECT) is currently offered as a treatment in Europe for locoregional or metastatic melanoma with cutaneous lesions. However, the role of surgery and other forms of electroporation in melanoma requires further evaluation. Two reviewers used two databases to conduct a literature search and review, and 51 publications related to electroporation with chemotherapy, immunotherapy, or gene delivery were found. ECT appears to be effective in reducing tumor burden for surgical resection, replacing surgical intervention with evidence of complete regression in some lesions, and inducing both local and systemic immune effects. These immune effects are pronounced when ECT is combined with immunotherapy, with a statistically significant improvement in overall survival (OS). Other forms of electroporation, such as those using calcium chloride, an IL-12 plasmid, and vaccination, require further study. However, IL-12 plasmid electroporation may be inferior to ECT based on the evidence available. Furthermore, irradiation of the tumor prior to ECT treatment is negatively correlated with local response. Access to ECT is restricted in the US and requires further evaluation. More randomized controlled trials of ECT and electroporation treatment in locoregional melanoma are recommended.

  View details for DOI 10.3390/jcm13133828

  View details for PubMedID 38999394

• Digital assessment of tertiary lymphoid structures and therapeutic responses in gastric cancer: A multi-centric retrospective study. International journal of surgery (London, England) Chen, Y., Sun, Z., Yin, J., Ahmad, M. U., Zhou, Z., Feng, W., Yang, F., Zhou, K., Xie, J., Bie, C., Chen, H., Jiang, Y. 2024

  Abstract

  Tertiary lymphoid structures (TLSs) are associated with favorable prognosis and enhanced response to anti-cancer therapy. A digital assessment of TLSs could provide an objective alternative that mitigates variability inherent in manual evaluation. This study aimed to develop and validate a digital gene panel based on biological prior knowledge for assessment of TLSs, and further investigate its associations with survival and multiple anti-cancer therapies.The present study involved 1,704 patients with gastric cancer from seven cancer centers. TLSs were identified morphologically through hematoxylin-and-eosin staining. We further developed a digital score based on targeted gene expression profiling to assess TLSs status, recorded as gene signature of tertiary lymphoid structures (gsTLS). For enhanced interpretability, we employed the SHapley Additive exPlanation (SHAP) analysis to elucidate its contribution to the prediction. We next evaluated the signature's associations with prognosis, and investigated its predictive accuracy for multiple anti-cancer therapies, including adjuvant chemotherapy and immunotherapy.The gsTLS panel with nine gene features achieved high accuracies in predicting TLSs status in the training, internal and external validation cohorts (area under the curve, range: 0.729-0.791). In multivariable analysis, gsTLS remained an independent predictor of disease-free and overall survival (hazard ratio, range: 0.346-0.743, all P < 0.05) after adjusting for other clinicopathological variables. SHAP analysis highlighted gsTLS as the strongest predictor of TLSs status compared with clinical features. Importantly, patients with high gsTLS (but not those with low gsTLS) exhibited substantial benefits from adjuvant chemotherapy (P < 0.05). Furthermore, we found that the objective response rate to anti-programmed cell death protein 1 (anti-PD-1) immunotherapy was significantly higher in the high-gsTLS group (40.7%) versus the low-gsTLS group (5.6%, P = 0.036), and the diagnosis was independent from Epstein-Barr virus (EBV), tumor mutation burden (TMB), and programmed cell death-ligand 1 (PD-L1) expression.The gsTLS digital panel enables accurate assessment of TLSs status, and provides information regarding prognosis and responses to multiple therapies for gastric cancer.

  View details for DOI 10.1097/JS9.0000000000001834

  View details for PubMedID 38884256

• Distal Pancreatectomy With and Without Celiac Axis Resection for Adenocarcinoma: A Comparison in the Era of Neoadjuvant Therapy Daniel, S. K., Hironaka, C., Ahmad, M., Delitto, D., Dua, M., Lee, B., Norton, J., Visser, B., Poultsides, G. SPRINGER. 2024: S202-S203

  View details for Web of Science ID 001185577500451

• Macrophage function over phenotype determines sensitization to immunotherapy Lee, D., Sharma, S., Serasanambati, M., Ahmad, M., Larijani, B., Kirane, A. SPRINGER. 2024: S214

  View details for Web of Science ID 001185577500478

• Toward the Development of Functional Biomarker Assays: Analysis of Neoadjuvant Intralesional Oncolytic Virus Response in High-Risk Stage II Melanoma Kirane, A., Lee, D., Ahmad, M., Sharma, S., Serasanambati, M., Lowe, M., Applebee, C., Safrygina, E., Swetter, S., Reddy, S., Warner, A., Funchain, P., Wang, J., Levy, R., Larijani, B., Maverakis, E. SPRINGER. 2024: S33-S34

  View details for Web of Science ID 001185577500066

• Comprehensive assessment of immune context and immunotherapy response via noninvasive imaging in gastric cancer. The Journal of clinical investigation Sun, Z., Zhang, T., Ahmad, M. U., Zhou, Z., Qiu, L., Zhou, K., Xiong, W., Xie, J., Zhang, Z., Chen, C., Yuan, Q., Chen, Y., Feng, W., Xu, Y., Yu, L., Wang, W., Yu, J., Li, G., Jiang, Y. 2024

  Abstract

  The tumor immune microenvironment can provide prognostic and therapeutic information. We aimed to develop noninvasive imaging biomarkers from computed tomography (CT) for comprehensive evaluation of immune context, and investigate their associations with prognosis and immunotherapy response in gastric cancer (GC).This study involved 2,600 GC patients of nine independent cohorts. We developed and validated two CT imaging biomarkers [lymphoid radiomics score (LRS) and myeloid radiomics score (MRS)] for evaluating the immunohistochemistry (IHC)-derived lymphoid and myeloid immune context respectively, and then integrated them into a combined imaging biomarker [LRS/MRS: low(-) or high(+)] with four radiomics immune subtypes: 1(-/-), 2(+/-), 3(-/+), and 4(+/+). We further evaluated the imaging biomarkers' predictive values on prognosis and immunotherapy response.The developed imaging biomarkers (LRS and MRS) had a high accuracy in predicting lymphoid (AUC range: 0.765-0.773) and myeloid (AUC range: 0.736-0.750) immune context. Furthermore, same as IHC-derived immune context, two imaging biomarkers (HR range: 0.240-0.761 for LRS; 1.301-4.012 for MRS) and the combined biomarker were independent predictors for disease-free and overall survival in the training and all validation cohorts (all P<0.05). In addition, patient with high LRS or low MRS may benefit more from immunotherapy (P<0.001). Furthermore, a highly heterogeneous outcome on objective response rate was observed in four imaging subtypes: 1(-/-) with 27.3%, 2(+/-) with 53.3%, 3(-/+) with 10.2%, and 4(+/+) with 30.0% (P<0.0001).The noninvasive imaging biomarkers could accurately evaluate the immune context, and provide information regarding prognosis and immunotherapy for GC.None.

  View details for DOI 10.1172/JCI175834

  View details for PubMedID 38271117

• Angioembolization for splenic injuries: does it help? Retrospective evaluation of grade III–V splenic injuries at two level I trauma centers Trauma & Acute Care Open Ahmad, M., Lee, D., Tennakoon, L., Chao, T. E., Spain, D., Staudenmayer, K. 2024; 9

  View details for DOI 10.1136/tsaco-2023-001240

• Computational pathology approach for prognostic advancements and therapeutic benefits in gastrointestinal cancer: A multi-centric retrospective study American Association for Cancer Research Zhang, T., Sun, Z., Ahmad, M., Islam, M. T., Yang, F., Li, Z., Jiang, Y. 2024

  View details for DOI 10.1158/1538-7445.AM2024-4939

• Single cell analysis of melanoma reveals a prognostic myeloid cell associated with survival in melanoma with brain metastases American Association for Cancer Research Ahmad, M., Heo, L., Nair, R. V., Sharma, S., Kirane, A. 2024

  View details for DOI 10.1158/1538-7445.AM2024-6865

• Biology-guided deep learning predicts prognosis and cancer immunotherapy response. Nature communications Jiang, Y., Zhang, Z., Wang, W., Huang, W., Chen, C., Xi, S., Ahmad, M. U., Ren, Y., Sang, S., Xie, J., Wang, J. Y., Xiong, W., Li, T., Han, Z., Yuan, Q., Xu, Y., Xing, L., Poultsides, G. A., Li, G., Li, R. 2023; 14 (1): 5135

  Abstract

  Substantial progress has been made in using deep learning for cancer detection and diagnosis in medical images. Yet, there is limited success on prediction of treatment response and outcomes, which has important implications for personalized treatment strategies. A significant hurdle for clinical translation of current data-driven deep learning models is lack of interpretability, often attributable to a disconnect from the underlying pathobiology. Here, we present a biology-guided deep learning approach that enables simultaneous prediction of the tumor immune and stromal microenvironment status as well as treatment outcomes from medical images. We validate the model for predicting prognosis of gastric cancer and the benefit from adjuvant chemotherapy in a multi-center international study. Further, the model predicts response to immune checkpoint inhibitors and complements clinically approved biomarkers. Importantly, our model identifies a subset of mismatch repair-deficient tumors that are non-responsive to immunotherapy and may inform the selection of patients for combination treatments.

  View details for DOI 10.1038/s41467-023-40890-x

  View details for PubMedID 37612313

  View details for PubMedCentralID PMC10447467

• Benchmarks and Geographic Differences in Gallbladder Cancer Surgery: An International Multicenter Study. Annals of surgical oncology Vega, E. A., Newhook, T. E., Mellado, S., Ruzzenente, A., Okuno, M., De Bellis, M., Panettieri, E., Ahmad, M. U., Merlo, I., Rojas, J., De Rose, A. M., Nishino, H., Sinnamon, A. J., Donadon, M., Hauger, M. S., Guevara, O. A., Munoz, C., Denbo, J. W., Chun, Y. S., Tran Cao, H. S., Sanchez Claria, R., Tzeng, C. D., De Aretxabala, X., Vivanco, M., Brudvik, K. W., Seo, S., Pekolj, J., Poultsides, G. A., Torzilli, G., Giuliante, F., Anaya, D. A., Guglielmi, A., Vinuela, E., Vauthey, J. 2023

  Abstract

  BACKGROUND: High-quality surgery plays a central role in the delivery of excellent oncologic care. Benchmark values indicate the best achievable results. We aimed to define benchmark values for gallbladder cancer (GBC) surgery across an international population.PATIENTS AND METHODS: This study included consecutive patients with GBC who underwent curative-intent surgery during 2000-2021 at 13 centers, across seven countries and four continents. Patients operated on at high-volume centers without the need for vascular and/or bile duct reconstruction and without significant comorbidities were chosen as the benchmark group.RESULTS: Of 906 patients who underwent curative-intent GBC surgery during the study period, 245 (27%) were included in the benchmark group. These were predominantly women (n = 174, 71%) and had a median age of 64 years (interquartile range 57-70 years). In the benchmark group, 50 patients (20%) experienced complications within 90 days after surgery, with 20 patients (8%) developing major complications (Clavien-Dindo grade ≥ IIIa). Median length of postoperative hospital stay was 6 days (interquartile range 4-8 days). Benchmark values included ≥ 4 lymph nodes retrieved, estimated intraoperative blood loss ≤ 350 mL, perioperative blood transfusion rate ≤ 13%, operative time ≤ 332 min, length of hospital stay ≤ 8 days, R1 margin rate ≤ 7%, complication rate ≤ 22%, and rate of grade ≥ IIIa complications ≤ 11%.CONCLUSIONS: Surgery for GBC remains associated with significant morbidity. The availability of benchmark values may facilitate comparisons in future analyses among GBC patients, GBC surgical approaches, and centers performing GBC surgery.

  View details for DOI 10.1245/s10434-023-13531-2

  View details for PubMedID 37149547

• The Impact of Mesenchymal Transition and Macrophage Phenotype in Immunotherapy-Resistant Melanoma Ahmad, M., Han, B., Ju, A., Sun, B. J., Maverakis, E., Kirane, A. R. SPRINGER. 2023: S236

  View details for Web of Science ID 001046841200519

• The Role of AXL Tyrosine Kinase in the Melanoma Immune Microenvironment Sun, B., Ahmad, M., Gingrich, A. A., Walsh, A., Nielsen, R., Maverakis, E., Kirane, A. R. SPRINGER. 2022: 465

  View details for Web of Science ID 000789811800310

• Radiographic, Biochemical, or Pathologic Response to Neoadjuvant Chemotherapy in Resected Pancreatic Cancer: Which Is Best? Javadi, C., Chang, J., Forgo, E., Ahmad, M., Fisher, G. A., Chang, D. T., Delitto, D. J., Dua, M. M., Lee, B., Visser, B. C., Norton, J. A., Poultsides, G. A. SPRINGER. 2022: 351

  View details for Web of Science ID 000789811800041

• Neoadjuvant Intralesional Therapy for High Risk Stage II Melanoma Lowe, M. C., Ahmad, M., Sun, B., Gholami, S., Maverakis, E., Kirane, A. R. SPRINGER. 2022: 534

  View details for Web of Science ID 000789811800468

• Neoadjuvant Treatment Strategies for Resectable Proximal Gastric, Gastroesophageal Junction and Distal Esophageal Cancer. Cancers Ahmad, M. U., Javadi, C., Poultsides, G. A. 2022; 14 (7)

  Abstract

  Neoadjuvant treatment strategies for resectable proximal gastric, gastroesophageal junction (GEJ), and distal esophageal cancer have evolved over several decades. Treatment recommendations differ based on histologic type-squamous cell carcinoma (SCC) versus adenocarcinoma (AC)-as well as the exact location of the tumor. Recent and older clinical trials in this area were critically reviewed. Neoadjuvant chemoradiation with concurrent taxane- or fluoropyrimidine-based chemotherapy has an established role for both AC and SCC of the distal esophagus and GEJ. The use of perioperative chemotherapy for gastric AC is based on the FLOT4 and MAGIC trials; however, the utility of neoadjuvant chemoradiation in this setting requires further evaluation. Additional clinical trials evaluating chemotherapy, targeted therapy, immunotherapy, and radiation that are currently in process are highlighted, given the need for further disease control.

  View details for DOI 10.3390/cancers14071755

  View details for PubMedID 35406527

• Rare histologies in peritoneal carcinomatosis: a narrative review Digestive Medicine Research Ahmad, M., Gebregziabher, B., Lee, B. 2022; 5

  View details for DOI 10.21037/dmr-22-4

• Biology-guided deep learning predicts prognosis and cancer immunotherapy response Society for Immunotherapy of Cancer’s (SITC) 37th Annual Meeting Jiang, Y., Zhang, Z., Wang, W., Huang, W., Chen, C., Xi, S., Ahmad, M., Ren, Y., Sang, S., Xie, J., Xiong, W., Li, T., Han, Z., Yuan, Q., Xu, Y., Xing, L., Poultsides, G., Li, G., Li, R. 2022

  View details for DOI 10.1136/jitc-2022-SITC2022.1284

• Acute Colonic Pseudo-Obstruction After Posterior Spinal Fusion: A Case Report and Literature Review WORLD NEUROSURGERY Ahmad, M., Riley, K. D., Ridder, T. S. 2020; 142: 352-363

  Abstract

  Acute colonic pseudo-obstruction (ACPO) or Ogilvie's syndrome occurs in 0.22%-7% of patients undergoing surgery, with a mortality of up to 46%. ACPO increased median hospital days versus control in spinal surgery (14 vs. 6 days; P < 0.001). If defined as postoperative ileus, the incidence was 7%-13.4%. Postoperative ileus is associated with 2.9 additional hospital days and an $80,000 increase in cost per patient. We present a case of ACPO in an adult patient undergoing spinal fusion for correction of scoliosis and review the available literature to outline clinical characteristics and surgical outcomes.The patient was a 31-year-old woman with untreated advanced scoliosis with no history of neurologic issues. T2-L3 spinal instrumentation and fusion was completed. Plain abdominal radiography showed of dilated cecum 11 cm and the department of general surgery was consulted. Neostigmine administration was planned after conservative treatment failure after transfer to the intensive care unit. The patient was discharged home with no recurrence >60 days. Thirty cases were found in our literature review using PubMed and Embase databases and summarized.Of 30 cases reviewed, only 3 cases of ACPO were specific to patients undergoing spinal fusion for scoliosis. According to the literature, 20% of patients had resolution with conservative treatment, 40% with neostigmine, and 30% with surgical intervention. Other noninvasive treatments may have similar efficacy in preventing complications leading to surgical invention. Sixty clinical trials and 9 systematic reviews were summarized with an updated management algorithm.

  View details for DOI 10.1016/j.wneu.2020.07.013

  View details for Web of Science ID 000576459300120

  View details for PubMedID 32659357

• A predictive model for decreasing clinical no-show rates in a primary care setting INTERNATIONAL JOURNAL OF HEALTHCARE MANAGEMENT Ahmad, M., Zhang, A., Mhaskar, R. 2021; 14 (3): 829-836

  View details for DOI 10.1080/20479700.2019.1698864

  View details for Web of Science ID 000501837900001

• A Systematic Review of Opt-out Versus Opt-in Consent on Deceased Organ Donation and Transplantation (2006-2016) WORLD JOURNAL OF SURGERY Ahmad, M., Hanna, A., Mohamed, A., Schlindwein, A., Pley, C., Bahner, I., Mhaskar, R., Pettigrew, G. J., Jarmi, T. 2019; 43 (12): 3161-3171

  Abstract

  Significant numbers of patients in the USA and UK die while waiting for solid organ transplant. Only 1-2% of deaths are eligible as donors with a fraction of the deceased donating organs. The form of consent to donation may affect the organs available. Forms of consent include: opt-in, mandated choice, opt-out, and organ conscription. Opt-in and opt-out are commonly practiced. A systematic review was conducted to determine the effect of opt-in versus opt-out consent on the deceased donation rate (DDR) and deceased transplantation rate (DTR).Literature searches of PubMed and EMBASE between 2006 and 2016 were performed. Research studies were selected based on certain inclusion criteria which include USA, UK, and Spain; compare opt-in versus opt-out; primary data analysis; and reported DDR or DTR. Modeled effect on US transplant activity was conducted using public data from Organ Procurement and Transplantation Network and Centers for Disease Control WONDER from 2006 to 2015.A total of 2400 studies were screened and six studies were included. Four studies reported opt-out consent increases DDR by 21-76% over 5-14 years. These studies compared 13-25 opt-out countries versus 9-23 opt-in countries. Three studies reported opt-out consent increases DTR by 38-83% over 11-13 years. These studies compared 22-25 opt-out versus 22-28 opt-in countries. Modeled opt-out activity on the USA resulted in 4753-17,201 additional transplants annually.Opt-out consent increases DDR and DTR and may be useful in decreasing deaths on the waiting list in the USA and other countries.PROSPERO CRD42019098759.

  View details for DOI 10.1007/s00268-019-05118-4

  View details for Web of Science ID 000501827500026

  View details for PubMedID 31428836

• Clinical Activity of Nivolumab for Human Papilloma Virus-Related Juvenile-Onset Recurrent Respiratory Papillomatosis ONCOLOGIST Creelan, B. C., Ahmad, M., Kaszuba, F. J., Khalil, F. K., Welsh, A. W., Ozdemirli, M., Grant, N. N., Subramaniam, D. S. 2019; 24 (6): 829-835

  Abstract

  Juvenile-onset recurrent respiratory papillomatosis (JO-RRP) is a human papilloma virus-mediated progressive benign neoplasm that affects children and young adults. Primary management consists of regular surgical debulking to maintain airway patency and vocal function. Like condyloma acuminata, JO-RRP is associated with immune dysregulation, and T cells isolated from papillomas express an anergic phenotype. Therefore, we hypothesized that programmed death protein 1 axis inhibition could stabilize tumor growth.We treated two patients with refractory JO-RRP using nivolumab, with the primary objective of assessing clinical activity. We explored baseline papilloma features using immunohistochemistry and comprehensive genomic profiling.Both patients experienced symptomatic improvement, and interval laryngoscopies revealed a reduction in papillomatosis burden. One patient has not required subsequent surgical debridement for almost 2 years. On pathologic examination of pretreatment papillomas from both cases, infiltrating T cells were evident in the papilloma stroma, and papilloma programmed death ligand 1 expression was absent. Papilloma mutational load ranged between three and six mutations per megabase for each case. From on-treatment biopsy tissue, a higher amount of intraepithelial T cells and programmed death ligand 1 expression were detected in the papilloma.Nivolumab appears to have promising activity in JO-RRP, and further clinical investigation with more patients in clinical trials is warranted.To the authors' knowledge, this article is the first report describing clinical activity with a programed cell death-1 (PD-1) inhibitor to treat a rare but detrimental type of respiratory tract epithelial neoplasm that afflicts young adults. Two patients were treated, and tumor features, such as mutational load, were examined with the intent to stimulate future hypotheses for translational research. The safety and activity of PD-1 inhibitors in this population still need to be corroborated in clinical trials and should not yet be adopted into clinical practice.

  View details for DOI 10.1634/theoncologist.2018-0505

  View details for Web of Science ID 000471906300043

  View details for PubMedID 30842242

  View details for PubMedCentralID PMC6656512

• Increasing Organ Supply in the US: A Systematic Review of Presumed Consent vs. Informed Consent (2006-2016) Ahmad, M., Hanna, A., Mohamed, A., Mhaskar, R., Jarmi, T., Schlindwein, A., Pley, C., Bahner, I. WILEY. 2017: 307

  View details for Web of Science ID 000404515702285