Publications by authors named "Sepideh Gholami"

45 Publications

Chemotherapy After Diagnosis of Malignant Bowel Obstruction is Associated with Superior Survival for Medicare Patients with Advanced Malignancy.

Ann Surg Oncol 2021 Apr 7. Epub 2021 Apr 7.

Division of Surgical Oncology, Department of Surgery, UC Davis Medical Center, University of California, Sacramento, CA, USA.

Background: Although malignant bowel obstruction (MBO) often is a terminal event, systemic therapies are advocated for select patients to extend survival. This study aimed to evaluate factors associated with receipt of chemotherapy after MBO and to determine whether chemotherapy after MBO is associated with survival.

Methods: This retrospective cohort study investigated patients 65 years of age or older with metastatic gastrointestinal, gynecologic, or genitourinary cancers who were hospitalized with MBO from 2008 to 2012 using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Fine and Gray models were used to identify factors associated with receipt of chemotherapy accounting for the competing risk of death. Cox models identified factors associated with overall survival.

Results: Of the 2983 MBO patients, 39% (n = 1169) were treated with chemotherapy after MBO. No differences in receipt of chemotherapy between the surgical and medical patients were found in the univariable analysis (subdistribution hazard ratio [SHR], 0.96; 95% confidence interval [CI], 0.86-1.07; p = 0.47) or multivariable analysis (SHR, 1.12; 95% CI, 1.00-1.26; p = 0.06). Older age, African American race, medical comorbidities, non-colorectal and non-ovarian cancer diagnoses, sepsis, ascites, and intensive care unit stays were inversely associated with receipt of chemotherapy after MBO (p < 0.05). Chemotherapy with surgery was associated with longer survival than surgery (adjusted hazard ratio [aHR], 2.97; 95% CI, 2.65-3.34; p < 0.01) or medical management without chemotherapy (aHR, 4.56; 95% CI, 4.04-5.14; p < 0.01). Subgroup analyses of biologically diverse cancers (colorectal, pancreatic, and ovarian) showed similar results, with greater survival related to chemotherapy (p < 0.05).

Conclusions: Chemotherapy plays an integral role in maximizing oncologic outcome for select patients with MBO. The data from this study are critical to optimizing multimodality care for these complex patients.
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http://dx.doi.org/10.1245/s10434-021-09831-0DOI Listing
April 2021

Advances in Modeling the Immune Microenvironment of Colorectal Cancer.

Front Immunol 2020 10;11:614300. Epub 2021 Feb 10.

Department of Surgery, University of California, Davis, Sacramento, CA, United States.

Colorectal cancer (CRC) is the third most common cancer and second leading cause of cancer-related death in the US. CRC frequently metastasizes to the liver and these patients have a particularly poor prognosis. The infiltration of immune cells into CRC tumors and liver metastases accurately predicts disease progression and patient survival. Despite the evident influence of immune cells in the CRC tumor microenvironment (TME), efforts to identify immunotherapies for CRC patients have been limited. Here, we argue that preclinical model systems that recapitulate key features of the tumor microenvironment-including tumor, stromal, and immune cells; the extracellular matrix; and the vasculature-are crucial for studies of immunity in the CRC TME and the utility of immunotherapies for CRC patients. We briefly review the discoveries, advantages, and disadvantages of current and model systems, including 2D cell culture models, 3D culture systems, murine models, and organ-on-a-chip technologies.
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http://dx.doi.org/10.3389/fimmu.2020.614300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902698PMC
February 2021

Is minimally invasive surgery of lesions in the right superior segments of the liver justified? A multi-institutional study of 245 patients.

J Surg Oncol 2020 Dec 16;122(7):1428-1434. Epub 2020 Aug 16.

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.

Background: Controversy exists regarding the safety and feasibility of minimally invasive resection for lesions in segments 7 or 8. We compare outcomes of minimally invasive surgery (MIS) and Open parenchymal sparing liver resections at two high-volume centers.

Methods: From 2003 to 2016 we identified patients who underwent MIS or Open resections for lesions in segments 7 or 8 at two institutions (MSKCC and SGH). Outcomes were compared using univariate and multivariate analyses.

Results: Two-hundred and forty-five patients underwent resection of lesions in segments 7 or 8 (MIS 30% and Open 70%). Compared to the Open group, the MIS group had longer operative time (223 ± 88 vs 188 ± 72 minutes, P = .003), lower blood loss (297 ± 287 vs 448 ± 670 mL, P = .03), and shorter mean length of stay (5.2 ± 7.4 vs 8.3 ± 11.7 days, P < .001), which remained significant on multivariate analysis. No differences in Pringle time, rate of postoperative complications, or R0 resections were detected.

Conclusions: With appropriately selected patients treated by experienced MIS hepatopancreatobiliary surgeons, MIS resection of segments 7 or 8 is safe with similar rates of complications and R0 resections, with significantly less blood loss and shorter length of stay.
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http://dx.doi.org/10.1002/jso.26154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978501PMC
December 2020

Two-Stage Hepatectomy for Bilateral Colorectal Liver Metastases: A Multi-institutional Analysis.

Ann Surg Oncol 2021 Mar 3;28(3):1457-1465. Epub 2021 Jan 3.

Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.

Background: Two-stage hepatectomy (TSH) is an important tool in the management of bilateral colorectal liver metastases (CRLM). This study sought to examine the presentation, management, and outcomes of patients completing TSH in major hepatobiliary centers in the United States (US).

Methods: A retrospective review from five liver centers in the US identified patients who completed a TSH procedure for bilateral CRLM.

Results: From December 2000 to March 2016, a total of 196 patients were identified. The majority of procedures were performed using an open technique (n = 194, 99.5%). The median number of tumors was 7 (range 2-33). One-hundred and twenty-eight (65.3%) patients underwent portal vein embolization. More patients received chemotherapy prior to the first stage than chemotherapy administration preceding the second stage (92% vs. 60%, p = 0.308). Median overall survival (OS) was 50 months, with a median follow-up of 28 months (range 2-143). Hepatic artery infusion chemotherapy was administered to 64 (32.7%) patients with similar OS as those managed without an infusion pump (p = 0.848). Postoperative morbidity following the second-stage resection was 47.4%. Chemotherapy prior to the second stage did not demonstrate an increased complication rate (p = 0.202). Readmission following the second stage was 10.3% and was associated with a decrease in disease-free survival (p = 0.003). OS was significantly decreased by positive resection margins and increased estimated blood loss (EBL; p = 0.036 and p = 0.05, respectively).

Conclusion: This is the largest TSH series in the US and demonstrates evidence of safety and feasibility in the management of bilateral CRLM. Outcomes are influenced by margin status and operative EBL.
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http://dx.doi.org/10.1245/s10434-020-09459-6DOI Listing
March 2021

Impact of Primary Tumor Laterality on Adjuvant Hepatic Artery Infusion Pump Chemotherapy in Resected Colon Cancer Liver Metastases: Analysis of 487 Patients.

Ann Surg Oncol 2020 Nov 23. Epub 2020 Nov 23.

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Background: Hepatic artery infusion (HAI) chemotherapy is associated with overall survival (OS) in patients with resected colon cancer liver metastases (CLM). The prognostic impact of primary tumor location in CLM following hepatic resection in patients receiving regional HAI is unknown. This study seeks to investigate the prognostic impact of HAI in relation to laterality in this patient population.

Methods: Consecutive patients with resected CLM, with known primary tumor site treated with and without HAI, were reviewed from a prospective institutional database. Correlations between HAI, laterality, other clinicopathological factors, and survival were analyzed, and Cox proportional hazard regression was used to determine whether laterality was an independent prognostic factor.

Results: From 1993 to 2012, 487 patients [182 with right colon cancer (RCC), 305 with left colon cancer (LCC)] were evaluated with a median follow-up of 6.5 years. Fifty-seven percent (n = 275) received adjuvant HAI. Patients with RCC had inferior 5-year OS compared with LCC (56% vs. 67%, P = 0.01). HAI was associated with improved 5-year OS in both RCC (68% vs. 45%; P < 0.01) and LCC (73% vs. 55%; P < 0.01). On multivariable analysis, HAI remained associated with improved OS (HR 0.52; 95% CI 0.39-0.70; P < 0.01) but primary tumor site did not (HR 0.83; 95% CI 0.63-1.11; P = 0.21). Additional significant prognostic factors on multivariable analysis included age, number of tumors, node-positive primary, positive margins, RAS mutation, two-stage hepatectomy, and extrahepatic disease. Cox proportional hazard regression determined no significant interaction between HAI and laterality on OS [parameter estimate (SEM), 0.12 (0.28); P = 0.67].

Conclusions: Our data show an association of adjuvant HAI and increased OS in patients who underwent curative hepatectomy, irrespective of primary tumor location. Laterality should therefore not impact decision-making when offering adjuvant HAI.
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http://dx.doi.org/10.1245/s10434-020-09369-7DOI Listing
November 2020

Management of early hepatocellular carcinoma: results of the Delphi consensus process of the Americas Hepato-Pancreato-Biliary Association.

HPB (Oxford) 2020 Sep 29. Epub 2020 Sep 29.

Department of Surgery, City of Hope, Duarte, CA, USA. Electronic address:

Background: There are many potential treatment options for patients with early stage hepatocellular carcinoma (HCC) and practice patterns vary widely. This project aimed to use a Delphi conference to generate consensus regarding the management of small resectable HCC.

Methods: A base case was established with review by members of AHPBA Research Committee. The Delphi panel of experts reviewed the literature and scored clinical case statements to identify areas of agreement and disagreement. Following initial scoring, discussion was undertaken, questions were amended, and scoring was repeated. This cycle was repeated until no further likelihood of reaching consensus existed.

Results: The panel achieved agreement or disagreement consensus regarding 27 statements. The overarching themes included that resection, ablation, transplantation, or any locoregional therapy as a bridge to transplant were all appropriate modalities for early or recurrent HCC. For larger lesions, consensus was reached that radiofrequency ablation and microwave ablation were not appropriate treatments.

Conclusion: Using a validated system for identifying consensus, an expert panel agreed that multiple treatment modalities are appropriate for early stage HCC. These consensus guidelines are intended to help guide physicians through treatment modalities for early HCC; however, clinical decisions should continue to be made on a patient-specific basis.
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http://dx.doi.org/10.1016/j.hpb.2020.09.013DOI Listing
September 2020

Adjuvant Hepatic Artery Infusion Chemotherapy is Associated With Improved Survival Regardless of KRAS Mutation Status in Patients With Resected Colorectal Liver Metastases: A Retrospective Analysis of 674 Patients.

Ann Surg 2020 08;272(2):352-356

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.

Objective: To investigate the impact of adjuvant hepatic artery infusion (HAI) in relation to KRAS mutational status in patients with resected colorectal cancer liver metastases (CRLM).

Background: Patients with KRAS-mutated CRLM have worse outcomes after resection. Adjuvant HAI chemotherapy improves overall survival after liver resection.

Methods: Patients with resected CRLM treated at MSKCC with and without adjuvant HAI who had available KRAS status (wild-type, WT; mutated, MUT) were reviewed from a prospectively maintained institutional database. Correlations between KRAS status, adjuvant HAI, clinical factors, and outcomes were analyzed. Cox proportional hazard model was used to adjust for confounders.

Results: Between 1993 and 2012, 674 patients (418 KRAS-WT, 256 MUT) with a median follow up of 6.5 years after resection were evaluated. Fifty-four percent received adjuvant HAI. Tumor characteristics (synchronous disease, number of lesions, clinical-risk score, 2-stage hepatectomy) were significantly worse in the HAI group; however, there were more patients with resected extrahepatic metastases in the no-HAI group. In KRAS-WT tumors, 5-year survival was 78% for patients treated with HAI versus 57% for patients without HAI [hazard ratio (HR) 0.51, P < 0.001]. In KRAS-MUT tumors, 5-year survival was 59% for patients treated with HAI versus 40% for patients without HAI (HR 0.56, P < 0.001). On multivariate analysis, HAI remained associated with improved OS (HR 0.53, P < 0.002) independent of KRAS status and other clinicopathologic factors.

Conclusion: Adjuvant HAI after resection of CRLM is independently associated with improved outcomes regardless of KRAS mutational status. Adjuvant HAI may mitigate the worse outcomes seen in patients with resectable KRAS-MUT CRLM.
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http://dx.doi.org/10.1097/SLA.0000000000003248DOI Listing
August 2020

Neoadjuvant Immunotherapy-Based Systemic Treatment in MMR-Deficient or MSI-High Rectal Cancer: Case Series.

J Natl Compr Canc Netw 2020 07;18(7):798-804

1UC Davis Comprehensive Cancer Center, Sacramento, California.

Treatment options for locally advanced rectal cancer have continued to consist largely of chemotherapy, chemoradiation, and/or surgical resection. For patients who are unable to undergo these therapeutic modalities or who do not to experience a response to them, treatment options are limited. We report 3 cases of mismatch repair-deficient (dMMR) locally advanced adenocarcinoma of the rectum that showed significant response with neoadjuvant immunotherapy-based systemic treatment. The first patient was not eligible for standard therapy because of a history of radiotherapy to the prostate with concurrent comorbidities and therefore received single-agent pembrolizumab. The second patient did not respond to total neoadjuvant chemoradiation and subsequently received combined nivolumab and ipilimumab. The third patient had a known family history of Lynch syndrome and presented with locally advanced rectal cancer and a baseline carcinoembryonic antigen level of 1,566 ng/mL. She was treated using neoadjuvant pembrolizumab and FOLFOX (folinic acid, fluorouracil, oxaliplatin). In this small series, we suggest that single-agent and combined-modality neoadjuvant immunotherapy/chemotherapy appear to be safe and effective treatment options for patients with (dMMR) locally advanced rectal cancer. Our findings encourage further studies to investigate the role of neoadjuvant immunotherapy as a viable treatment strategy in this population.
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http://dx.doi.org/10.6004/jnccn.2020.7558DOI Listing
July 2020

The Role of Palliative Surgery for Malignant Bowel Obstruction and Perforation in Advanced Microsatellite Instability-High Colorectal Carcinoma in the Era of Immunotherapy: Case Report.

Front Oncol 2020 21;10:581. Epub 2020 Apr 21.

Division of Hematology and Oncology, Department of Medicine, University of California, Davis, Sacramento, CA, United States.

The role of palliative surgery in the management of acute complications in patients with disseminated malignancy remains controversial given the complexity of assessing acute surgical risk and long-term oncologic outcome. With the emergence of checkpoint blockade immunotherapy, there appears to be an increasing role for historically palliative procedures as a bridge to systemic immunotherapy. This is especially evident in advanced microsatellite instability-high (MSI-H) colorectal cancer where malignant obstruction and fistula formation are more common and where immunotherapy with checkpoint blockade (anti-PD-1/PD-L1, anti-CTLA-4) has a high response rate with potential for favorable oncologic outcomes. We present a series of three patients with MSI-H metastatic colorectal cancer complicated by malignant bowel obstruction and fistula formation, who having progressed on standard chemotherapy, underwent palliative intervention as a bridge to immune checkpoint blockade with durable and clinically meaningful anti-cancer responses. These cases highlight the need to re-evaluate the role of historically palliative operations in the setting of disease progression for immunotherapy-responsive tumors.
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http://dx.doi.org/10.3389/fonc.2020.00581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186327PMC
April 2020

Elderly Age Is Associated With More Conservative Treatment of Invasive Melanoma.

Anticancer Res 2020 May;40(5):2895-2903

Division of Surgical Oncology, Department of Surgery, University of California, Davis Medical Center, Sacramento, CA, U.S.A.

Background/aim: Competing mortality risks complicate treatment of elderly melanoma patients potentially leading to conservative management, including no sentinel lymph node biopsy. As systemic immunotherapy offers justification for nodal evaluation, we examined treatment trends among elderly melanoma patients.

Patients And Methods: We performed a National Cancer Database analysis of melanoma patients from 2004-2015. Patients were categorized by age (elderly ≥80-years-old). Multivariable logistic regression analyses were performed comparing characteristics and treatment by age.

Results: Of 187,814 patients, 2.7% were 1-25, 11.6% were 26-40, 46.6% were 41-64, 28.8% were 65-79, and 10.3% were ≥80-years-old with clinicopathologic and treatment differences between age cohorts. Nodal surgery was least common among elderly patients (43.1% vs. 60.7-69.8%, p<0.0001). For stage III, immunotherapy was least common among the elderly (p<0.0001), but associated with greater survival (HR=0.52, 95%CI=0.32-0.84, p=0.008).

Conclusion: Elderly melanoma patients were often treated conservatively, including no nodal evaluation, concerning for the potential undertreatment of this population.
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http://dx.doi.org/10.21873/anticanres.14266DOI Listing
May 2020

Pancreaticoportal Fistula Causing Hepatic Necrosis Treated With Pancreatic Duct Stenting.

Am J Gastroenterol 2020 12;115(12):1933

Division of Surgical Oncology, Department of Surgery, University of California, Davis, USA.

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http://dx.doi.org/10.14309/ajg.0000000000000554DOI Listing
December 2020

EGFR antibodies in resectable metastatic colorectal liver metastasis: more harm than benefit?

Lancet Oncol 2020 03 31;21(3):324-326. Epub 2020 Jan 31.

West Cancer Center and Research Institute, Germantown, TN, USA.

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http://dx.doi.org/10.1016/S1470-2045(20)30003-6DOI Listing
March 2020

Shifting the Treatment Paradigm for Pancreaticoportal Fistula Causing Hepatic Necrosis.

Dig Dis Sci 2020 07;65(7):1955-1959

Division of Surgical Oncology, Department of Surgery, University of California, 2279 45th Street, Davis, Sacramento, CA, 95817, USA.

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http://dx.doi.org/10.1007/s10620-020-06045-4DOI Listing
July 2020

The state of hepatic artery infusion chemotherapy in the management of metastatic colorectal cancer to the liver.

Chin Clin Oncol 2019 Oct;8(5):54

Division of Surgical Oncology, University of California Davis Cancer Center, Sacramento, CA, USA.

Hepatic artery infusion (HAI) chemotherapy is a locoregional therapy for colorectal cancer liver metastasis that has been available since the 1980s. Multiple clinical trials have demonstrated the safety and efficacy of HAI with higher response rates compared to systemic chemotherapy alone. Clinical trials have shown the benefit of using HAI as a bridge to conversion to resection at a higher rate than systemic chemotherapy alone with rates as high as 60% in heavily pretreated patients. HAI in combination with systemic chemotherapy has also been associated with prolonged recurrence free survival and overall survival in the adjuvant setting. Specifically, the addition of HAI continues to show a benefit in prolonging overall survival, despite increased effectiveness of modern systemic chemotherapy (i.e., oxaliplatin and irinotecan). Lower recurrence and improved survival rates associated with HAI and systemic chemotherapy persist regardless of RAS mutational status.
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http://dx.doi.org/10.21037/cco.2019.09.01DOI Listing
October 2019

Effectiveness of the back school program on the low back pain and functional disability of Iranian nurse.

J Exerc Rehabil 2019 Feb 25;15(1):134-138. Epub 2019 Feb 25.

Department of Operating Room, School of Nursing and Midwifery, North Khorasan University of Medical Sciences, Bojnurd, Iran.

Low back pain (LBP) as a recurrent and costly health problem and one of the leading causes of disability, is common in nurses. It can have adverse effects on the quality of life of nurses and quality of care of patients. The aim of the study was to evaluate the effectiveness of Back School program on the LBP and functional disability of Iranian nurses. A quasi-experimental methodological design was utilized for this study. Participants were nurses with back pain who participated in the Back School program workshop and completed a self-report visual analogue scales and Roland-Morris Disability questionnaire that measuring LBP and functional disability. Data were analyzed descriptively and comparisons in LBP and functional disability made between groups with -test for pre-intervention and analysis of covariance for after intervention. Sixty-four participants (16 males, 48 females) completed this survey. The study participants' mean age was 38.9 ± 8.1 years in intervention group and 38.1 ± 8.2 in control group. There were no significant differences in terms of pain ( = 0.575) and disability scores ( = 0.844) before intervention. Although, the intervention led to a decrease in the functional ability and LBP scores of the nurses (<0.001) in the intervention group compared with that in the control group. Overall, Back School program as an educational strategy can reduce the LBP and functional disability in nurses. This program can be suitable for preventing of pain and functional disability among nurses working in hospital settings.
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http://dx.doi.org/10.12965/jer.1836542.271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416510PMC
February 2019

Laparoscopic Liver Resection Difficulty Score-a Validation Study.

J Gastrointest Surg 2019 03 12;23(3):545-555. Epub 2018 Nov 12.

Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, 20 College Road, Singapore, 169856, Singapore.

Objective(s): The technical complexity of laparoscopic liver resection (LLR) poses unique challenges distinct from open surgery. An objective scoring system was developed that preoperatively quantifies the difficulty of LRR to help guide surgeon decision-making regarding the feasibility and safety of minimally invasive approaches. The aim of this multiinstitutional study was to externally validate this scoring system.

Methods: Patients who underwent LLR at two institutions were reviewed. LLR difficulty score (LDS) was calculated based on patient, tumor, and anatomic characteristics by two independent, blinded hepatobiliary surgeons. Surrogates of case complexity (e.g., conversion rate, operative time) were used for validation of this index.

Results: From 2006 to 2016, 444 LLR were scored as low (n = 94), intermediate (n = 98), and high difficulty (n = 152) with respective conversion rates of 5.3%, 15.7%, and 25%. Cases of higher LDS correlated with larger mean blood loss (203 ml vs. 331 ml vs. 635 ml). Mean operative and Pringle maneuver used were associated with increasing LDS (155 min vs. 202 min vs. 315 min and 14.4% vs. 29.7% vs. 45.1% respectively). These operative surrogates of difficulty correlated significantly with the LDS (all p < 0.0001).

Conclusions: This comprehensive external validation of the LDS is robust and applicable in diverse patient populations. This LDS serves as a useful objective predictor of technical difficulty for LLR to help surgeons in selecting patients according to their individual operative experience and is valuable for preoperative risk estimation and stratification in randomized trials.
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http://dx.doi.org/10.1007/s11605-018-4036-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545446PMC
March 2019

Metastatic squamous cell carcinoma of known and unknown primary origin treated with axillary or inguinal lymphadenectomy.

Am J Surg 2018 11 20;216(5):963-968. Epub 2018 Jun 20.

Memorial Sloan Kettering Cancer Center, USA. Electronic address:

Background: Metastatic squamous cell carcinoma (SCC) to the axillary or inguinal lymph nodes from an unknown primary source is rarely encountered. We sought to evaluate a cohort of patients with metastatic SCC managed by lymphadenectomy to determine their survival and to determine which clinicopathologic factors were associated with outcome.

Methods: All patients undergoing axillary or inguinal lymphadenectomy for SCC at our institution were identified retrospectively. Patients were stratified by unknown primary (UP) vs known skin primary (KP) tumors. Pertinent data on patient, tumor, and treatment variables was collected.

Results: We identified 51 patients who met inclusion criteria. Of those, 20 patients (39%) had UP metastatic SCC and 31 patients (61%) had KP. The 5-year overall survival for UP was 65%, as compared to 49% for KP (p = 0.16). Cumulative incidence of recurrence was 46%. Cox regression failed to demonstrate a significant association between KP vs UP, HPV status, chemotherapy, or radiation with survival.

Conclusions: Nearly two-thirds of patients undergoing axillary or inguinal lymphadenectomy for metastatic SCC of unknown primary were alive five years following the procedure.
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http://dx.doi.org/10.1016/j.amjsurg.2018.06.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545876PMC
November 2018

Is Hepatectomy Justified for BRAF Mutant Colorectal Liver Metastases?: A Multi-institutional Analysis of 1497 Patients.

Ann Surg 2020 01;271(1):147-154

Department of Hepatobiliary Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.

Objective: To analyze clinical outcomes and prognostic variables of patients undergoing hepatic resection for BRAF mutant (BRAF-mut) colorectal liver metastases (CRLM).

Background: Outcomes following hepatectomy for BRAF-mut CRLM have not been well studied.

Methods: All patients who underwent hepatectomy for CRLM with complete resection and known BRAF status during 2001 to 2016 at 3 high-volume centers were analyzed.

Results: Of 4124 patients who underwent hepatectomy for CRLM, 1497 had complete resection and known BRAF status. Thirty-five (2%) patients were BRAF-mut, with 71% of V600E mutation. Compared with BRAF wild-type (BRAF-wt), BRAF-mut patients were older, more commonly presented with higher ASA scores, synchronous, multiple and smaller CRLM, underwent more major hepatectomies, but had less extrahepatic disease. Median overall survival (OS) was 81 months for BRAF-wt and 40 months for BRAF-mut patients (P < 0.001). Median recurrence-free survival (RFS) was 22 and 10 months for BRAF-wt and BRAF-mut patients (P < 0.001). For BRAF-mut, factors associated with worse OS were node-positive primary tumor, carcinoembryonic antigen (CEA) >200 μg/L, and clinical risk score (CRS) ≥4. Factors associated with worse RFS were node-positive primary tumor, ≥4 CRLM, and positive hepatic margin. V600E mutations were not associated with worse OS or RFS. A case-control matching analysis on prognostic clinicopathologic factors confirmed shorter OS (P < 0.001) and RFS (P < 0.001) in BRAF-mut.

Conclusions: Patients with resectable BRAF-mut CRLM are rare among patients selected for surgery and more commonly present with multiple synchronous tumors. BRAF mutation is associated with worse prognosis; however, long-term survival is possible and associated with node-negative primary tumors, CEA ≤ 200 μg/L and CRS < 4.
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http://dx.doi.org/10.1097/SLA.0000000000002968DOI Listing
January 2020

The effectiveness of clinical teaching of mental health courses in nursing using clinical supervision and Kirkpatrick's model.

Electron Physician 2018 Jan 25;10(1):6265-6272. Epub 2018 Jan 25.

Ph.D. Candidate in Nursing, Department of Nursing, School of Nursing and Midwifery, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Background: Clinical experience associated with the fear and anxiety of nursing students in the psychiatric unit. Mental health nursing instructors find it challenging to teach nursing students to deal with patients with mental disorders in an environment where they need to provide patient teaching and clinical decision-making based on evidence and new technology.

Objective: To measure the effectiveness of clinical teaching of mental health courses in nursing using clinical supervision and Kirkpatrick's model evaluation in the psychiatry unit of Imam Reza Hospital, Bojnurd, Iran.

Methods: This cross-sectional study was carried out from 2011 to 2016 on 76 nursing students from a university as part of a clinical mental health course in two semesters. The students were selected by a non-probable convenient sampling method. After completing their clinical education, each student responded to checklist questions based on the four-level Kirkpatrick's model evaluation and open questions relating to clinical supervision. Finally, all data was analyzed using the SPSS version 16.

Results: The students have evaluated clinical supervision as a useful approach, and appreciated the instructor's supportive behavior during teaching and imparting clinical skills. This has made them feel relaxed at the end of the clinical teaching course. In addition, in the evaluation through Kirkpatrick's model, more than 70% of the students have been satisfied with the method of conducting the teaching and average score of nursing students' attitude toward mental health students: Their mean self-confidence score was 18.33±1.69, and the mean score of their performance in the study was evaluated to be 93.74±5.3 from 100 points.

Conclusion: The results of clinical mental health teaching through clinical supervision and Kirkpatrick's model evaluation show that the satisfaction, self-esteem, attitude, and skill of nursing students are excellent, thereby portraying the effectiveness of clinical teaching. But this program still needs to be reformed. To establish long-term goals and obtain knowledge and clinical skills of nursing, it is recommended to develop a curriculum and evaluate it appropriately.
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http://dx.doi.org/10.19082/6265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5854003PMC
January 2018

Preoperative Stenting for Benign and Malignant Periampullary Diseases: Unnecessary if Not Harmful.

Surg Clin North Am 2018 Feb;98(1):37-47

Memorial Sloan Kettering Cancer Center, International Center, 1275 York Avenue, H-1203, New York, NY 10065, USA. Electronic address:

Preoperative biliary drainage (PBD) is often performed in patients with jaundice with the presumption that it will decrease the risk of postoperative complications. PBD carries its own risk of complications and, therefore, has been controversial. Multiple randomized controlled trials and metaanalyses have shown that PBD has significantly increased overall complications compared with surgery alone. As such, the routine application of PBD should be avoided except in a subset of clinical situations. This is discussed in detail in this article.
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http://dx.doi.org/10.1016/j.suc.2017.09.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6643266PMC
February 2018

Size and Location are the Most Important Risk Factors for Malignant Behavior in Resected Solitary Fibrous Tumors.

Ann Surg Oncol 2017 Dec 16;24(13):3865-3871. Epub 2017 Oct 16.

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Purpose: While previously thought to be clinically indolent, recent data suggest significant late metastatic capacity of solitary fibrous tumors (SFTs). We define prognostic factors for recurrence and disease-specific death (DSD) in resected primary SFTs.

Methods: Resected primary SFTs from 1982 to 2015 were identified from a prospective, single institutional database. Risk factors for local (LR) and distant recurrence (DR), and DSD were assessed using competing risk analysis.

Results: A total of 219 patients with median follow-up of 6.1 (0.1-22) years were included. Five- and 10-year cumulative DSD was 9 and 11%, respectively. Size greater than the median 8 cm, gender, location, and complete gross resection were significantly associated with DSD (p < 0.05). Five- and 10-year cumulative risk (CR) of LR was 4 and 7%, whereas 5- and 10-year CR of DR was 13 and 16%, respectively. LR was associated with location (p = 0.02) and tumor size (p = 0.02), and DR was associated with size (p < 0.01). Histopathologic classification did not predict long-term behavior with both malignant and benign tumors demonstrating capacity for DR and associated death. Tumors in the thoracic cavity and abdomen/retroperitoneum presented the greatest risk of DR (16 and 27% 10-year CR). On multivariate analysis, size ≥ 8 cm (hazard ratio 2.89, p = 0.05) and tumor location in chest or abdominal/retroperitoneal cavity (hazard ratio 2.68, p = 0.01) significantly impacted DSD.

Conclusions: Recurrence is highly associated with DSD and events occur as late as 16 years after initial presentation, including in patients with initially considered benign tumors. Patients with large (≥ 8 cm) tumors in the chest or abdominal/retroperitoneal cavity are at greatest risk.
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http://dx.doi.org/10.1245/s10434-017-6092-zDOI Listing
December 2017

Imaging Tunneling Membrane Tubes Elucidates Cell Communication in Tumors.

Trends Cancer 2017 10 14;3(10):678-685. Epub 2017 Sep 14.

Department of Cell Biology, Sloan-Kettering Institute, New York, NY 10021, USA.

Intercellular communication is a vital yet underdeveloped aspect of cancer pathobiology. This Opinion article reviews the importance and challenges of microscopic imaging of tunneling nanotubes (TNTs) in the complex tumor microenvironment. The use of advanced microscopy to characterize TNTs in vitro and ex vivo, and related extensions called tumor microtubes (TMs) reported in gliomas in vivo, has propelled this field forward. This topic is important because the identification of TNTs and TMs fills the gap in our knowledge of how cancer cells communicate at long range in vivo, inducing intratumor heterogeneity and resistance to treatment. Here we discuss the concept that TNTs/TMs fill an important niche in the ever-changing microenvironment and the role of advanced microscopic imaging to elucidate that niche.
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http://dx.doi.org/10.1016/j.trecan.2017.08.001DOI Listing
October 2017

Minimally Invasive Surgical Approaches to Gastric Resection.

Surg Clin North Am 2017 Apr 14;97(2):249-264. Epub 2017 Feb 14.

Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, H-1217, New York, NY 10065, USA.

Minimally invasive gastric resections carry several advantages, including less intraoperative blood loss, faster recovery time, reduced pain, and decreased hospital length of stay and quicker return to work. Numerous trials have proved that laparoscopic and robotic-assisted gastrectomy provides equivalent surgical and oncologic outcomes to open approaches. As with any minimally invasive approach, advanced minimally invasive training and good judgment by a surgeon are paramount in selecting patients in whom a minimally invasive approach is feasible. With increasing research in patient populations with more advanced disease, the indications are likely to continue to expand.
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http://dx.doi.org/10.1016/j.suc.2016.11.003DOI Listing
April 2017

Minimally Invasive Surgery: The Emerging Role in Gastric Cancer.

Surg Oncol Clin N Am 2017 04 4;26(2):193-212. Epub 2017 Feb 4.

Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, H-1217, New York, NY 10065, USA. Electronic address:

Minimally invasive surgical techniques are an emerging option in the staging and management of gastric cancer in the United States and elsewhere. Although much of the current knowledge about these approaches and their outcomes has been generated in Eastern countries, experience in the United States is growing. This article discusses both laparoscopic and robotic approaches to gastric cancer management. Important aspects of patient selection are emphasized. Surgical and oncologic outcomes are presented and compared with traditional open gastrectomy. Technical considerations are discussed along with comments on the learning curve to achieve proficiency in each approach.
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http://dx.doi.org/10.1016/j.soc.2016.10.001DOI Listing
April 2017

Total Gastrectomy for Hereditary Diffuse Gastric Cancer at a Single Center: Postsurgical Outcomes in 41 Patients.

Ann Surg 2017 12;266(6):1006-1012

*Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY †Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY ‡Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY §Department of Gastroenterology, Memorial Sloan Kettering Cancer Center, New York, NY ¶Department of Medicine, Clinical Genetics Service, Memorial Sloan Kettering Cancer Center, New York, NY.

Objective: The aim of this study was to describe postoperative outcomes of total gastrectomy at our institution for patients with hereditary diffuse gastric cancer (HDGC).

Background: HDGC, which is mainly caused by germline mutations in the E-cadherin gene (CDH1), renders a lifetime risk of gastric cancer of up to 70%, prompting a recommendation for prophylactic total gastrectomy.

Methods: A prospective gastric cancer database identified 41 patients with CDH1 mutation who underwent total gastrectomy during 2005 to 2015. Perioperative, histopathologic, and long-term data were collected.

Results: Of the 41 patients undergoing total gastrectomy, median age was 47 years (range 20 to 71). There were 14 men and 27 women, with 25 open operations and 16 minimally invasive operations. Median length of stay was 7 days (range 4 to 50). In total, 11 patients (27%) experienced a complication requiring intervention, and there was 1 peri-operative mortality (2.5%). Thirty-five patients (85%) demonstrated 1 or more foci of intramucosal signet ring cell gastric cancer in the examined specimen. At 16 months median follow-up, the median weight loss was 4.7 kg (15% of preoperative weight). By 6 to 12 months postoperatively, weight patterns stabilized. Overall outcome was reported to be "as expected" by 40% of patients and "better than expected" by 45%. Patient-reported outcomes were similar to those of other patients undergoing total gastrectomy.

Conclusion: Total gastrectomy should be considered for all CDH1 mutation carriers because of the high risk of invasive diffuse-type gastric cancer and lack of reliable surveillance options. Although most patients have durable weight loss after total gastrectomy, weights stabilize at about 6 to 12 months postoperatively, and patients report outcomes as being good to better than their preoperative expectations. No patients have developed gastric cancer recurrence after resections.
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http://dx.doi.org/10.1097/SLA.0000000000002030DOI Listing
December 2017

Recurrent Pyogenic Cholangitis: Got Stones?

Dig Dis Sci 2016 Nov 24;61(11):3147-3150. Epub 2015 Nov 24.

Division of Surgical Oncology, Department of Surgery, Stanford University School of Medicine, 300 Pasteur Drive, Suite H3680A, Stanford, CA, 94305, USA.

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http://dx.doi.org/10.1007/s10620-015-3973-5DOI Listing
November 2016

Double Rarities, Double Challenges: Extra-Mammary Paget's Disease and Anal Adenocarcinoma.

Dig Dis Sci 2016 Apr 2;61(4):996-9. Epub 2015 Aug 2.

Division of General Surgery, Department of Surgery, Stanford University, Stanford, CA, USA.

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http://dx.doi.org/10.1007/s10620-015-3819-1DOI Listing
April 2016

Number of Lymph Nodes Removed and Survival after Gastric Cancer Resection: An Analysis from the US Gastric Cancer Collaborative.

J Am Coll Surg 2015 Aug 5;221(2):291-9. Epub 2015 May 5.

Department of Surgery, Stanford Cancer Institute, Stanford University, Stanford, CA. Electronic address:

Background: Examination of at least 16 lymph nodes (LNs) has been traditionally recommended during gastric adenocarcinoma resection to optimize staging, but the impact of this strategy on survival is uncertain. Because recent randomized trials have demonstrated a therapeutic benefit from extended lymphadenectomy, we sought to investigate the impact of the number of LNs removed on prognosis after gastric adenocarcinoma resection.

Study Design: We analyzed patients who underwent gastrectomy for gastric adenocarcinoma from 2000 to 2012, at 7 US academic institutions. Patients with M1 disease or R2 resections were excluded. Disease-specific survival (DSS) was calculated using the Kaplan-Meier method and compared using log-rank and Cox regression analyses.

Results: Of 742 patients, 257 (35%) had 7 to 15 LNs removed and 485 (65%) had ≥16 LNs removed. Disease-specific survival was not significantly longer after removal of ≥16 vs 7 to 15 LNs (10-year survival, 55% vs 47%, respectively; p = 0.53) for the entire cohort, but was significantly improved in the subset of patients with stage IA to IIIA (10-year survival, 74% vs 57%, respectively; p = 0.018) or N0-2 disease (72% vs 55%, respectively; p = 0.023). Similarly, for patients who were classified to more likely be "true N0-2," based on frequentist analysis incorporating both the number of positive and of total LNs removed, the hazard ratio for disease-related death (adjusted for T stage, R status, grade, receipt of neoadjuvant and adjuvant therapy, and institution) significantly decreased as the number of LNs removed increased.

Conclusions: The number of LNs removed during gastrectomy for adenocarcinoma appears itself to have prognostic implications for long-term survival.
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http://dx.doi.org/10.1016/j.jamcollsurg.2015.04.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4654942PMC
August 2015

Leiomyosarcoma: One disease or distinct biologic entities based on site of origin?

J Surg Oncol 2015 Jun;111(7):808-12

Department of Surgery, Stanford University Medical Center, Stanford, California.

Background: Leiomyosarcoma (LMS) can originate from the retroperitoneum, uterus, extremity, and trunk. It is unclear whether tumors of different origin represent discrete entities. We compared clinicopathologic features and outcomes following surgical resection of LMS stratified by site of origin.

Methods: Patients with LMS undergoing resection at a single institution were retrospectively reviewed. Clinicopathologic variables were compared across sites. Survival was calculated using the Kaplan-Meier method and compared using log-rank and Cox regression analyses.

Results: From 1983 to 2011, 138 patients underwent surgical resection for LMS. Retroperitoneal and uterine LMS were larger, higher grade, and more commonly associated with synchronous metastases. However, disease-specific survival, recurrence-free survival, and recurrence patterns were not significantly different across the four sites. Synchronous metastases (HR 3.20, P < 0.001), but not site of origin, size, grade, or margin status, were independently associated with worse DSS. A significant number of recurrences and disease-related deaths were noted beyond 5 years.

Conclusions: Although larger and higher grade, retroperitoneal and uterine LMS share similar survival and recurrence patterns with their trunk and extremity counterparts. LMS of various anatomic sites may not represent distinct disease processes based on clinical outcomes. The presence of metastatic disease remains the most important prognostic factor for LMS.
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http://dx.doi.org/10.1002/jso.23904DOI Listing
June 2015