Mashaal Dhir

Preoperative Nomogram to Predict Risk of Perioperative Mortality Following Pancreatic Resections for Malignancy

IntroductionThe majority of pancreatic resections for malignancy are performed in older patients with major comorbidities. The aim of this study was to develop a preoperative nomogram based on the presence of comorbidities to predict risk of perioperative mortality.Materials and MethodsThe National Inpatient Sample database was queried to identify patients that underwent pancreatectomy for malignancy. The preoperative comorbidities identified as predictors were used, and a nomogram was created. Sample A (2000–2004) was utilized to develop the model, and sample B (2005) was utilized to validate this model.ResultsThe overall actual observed perioperative mortality rate for samples A and B was 6.3% and 5.2%, respectively. The mean total points calculated for sample A by the nomogram was 131.7 that translates to a nomogram-predicted mortality rate of 4.9%, which is similar to the actual mortality. The mean total points for sample B was 128.1, which translates to a nomogram-predicted mortality rate of 4.6%. The similarity of mortality rates as predicted by the nomogram and a concordance index of 0.76 shows good agreement between the data and the nomogram.ConclusionThis preoperative nomogram has been shown to accurately predict the risk of perioperative mortality following pancreatectomy for malignancy.

History of pancreaticoduodenectomy: early misconceptions, initial milestones and the pioneers.

Pancreaticoduodenectomy is one of the most challenging surgical procedures which requires the highest level of surgical expertise. This procedure has constantly evolved over the years through the meticulous efforts of a number of surgeons before reaching its current state. This review navigates through some of the early limitations and misconceptions and highlights the initial milestones which laid the foundation of this procedure. The current review also provides a few excerpts from the lives and illuminates on some of the seminal contributions of the three great surgeons: William Stewart Halsted, Walther Carl Eduard Kausch and Allen Oldfather Whipple. These surgeons pioneered the nascent stages of this procedure and paved the way for the modern day pancreaticoduodenectomy.

Surgical Management of Liver Metastases From Colorectal Cancer

Surgical resection remains one of the major curative treatment options available to patients with colorectal liver metastases. Surgery and chemotherapy form the backbone of the treatment in patients with colorectal liver metastases. With more effective chemotherapy regimens being available, the optimal timing and sequencing of treatments are important. A multidisciplinary approach with the involvement of medical oncologists and surgical oncologists from the beginning is crucial. Identification of the clinical and molecular prognostic factors may help personalize the treatment approaches for these patients. This article provides an overview of the surgical management of colorectal liver metastases.

Neoadjuvant treatment of Dermatofibrosarcoma Protuberans of pancreas with Imatinib: case report and systematic review of literature

Dermatofibrosarcoma Protuberans (DFSP) is a rare skin tumor, characterized by frequent local recurrence but is seldom metastatic. It is histologically characterized by storiform arrangement of spindle cells. Cytogenetically, most tumors are characterized by translocation 17:22 leading to overexpression of tyrosine kinase PDGFB which can be targeted with tyrosine kinase inhibitor, Imatinib. We describe the first case of unresectable pancreatic metastases from DFSP treated with neoadjuvant Imatinib and subsequently R0 metastectomy. Additionally, a comprehensive systematic review of DFSP pancreatic metastases and the current published data on the use of Imatinib in DFSP is summarized.

External validation of a pre-operative nomogram predicting peri-operative mortality risk after liver resections for malignancy

AIM A pre-operative nomogram using a population-based database to predict peri-operative mortality risk after liver resections for malignancy has recently been developed. The aim of the present study was to perform an external validation of the nomogram using data from a high volume institution. METHODS The National Inpatient Sample (NIS) database (2000-2004) was used initially to construct the nomogram. The dataset for external validation was obtained from a high volume centre specializing in hepatobiliary surgery. Validation was performed using calibration plots and concordance index. RESULTS A total of 794 patients who underwent liver resection from the years 2000-2010 at the external institute were included in the validation set with an observed mortality rate of 1.6%. The mean total points for this sample of patients was 124.9 [standard error (SE) 1.8, range 0-383] which translates to a nomogram predicted mortality rate of 1.5%, similar to the actual observed overall mortality rate. The nomogram concordance index was 0.65 [95% confidence interval (CI) 0.46-0.82] and calibration plots stratified by quartiles revealed good agreement between the predicted and observed mortality rates. CONCLUSIONS The present study provides an external validation of the pre-operative nomogram to predict the risk of peri-operative mortality after liver resection for malignancy.

Robotic assisted placement of hepatic artery infusion pump is a safe and feasible approach.

Hepatic artery infusion (HAI) chemotherapy can be combined with systemic chemotherapy for the treatment of isolated unresectable colorectal liver metastases (IU‐CRLM) and intrahepatic cholangiocarcinoma (U‐ICC). However, HAI pump placement requires a major laparotomy that may be associated with morbidity. We hypothesized that the computer‐assisted robotic platform would be well suited for this procedure and report the first single institutional case series of robotic assisted HAI pump placement for primary and secondary malignancies of the liver.

Impact of genomic profiling on the treatment and outcomes of patients with advanced gastrointestinal malignancies

The impact of genomic profiling on the outcomes of patients with advanced gastrointestinal (GI) malignancies remains unknown. The primary objectives of the study were to investigate the clinical benefit of genomic‐guided therapy, defined as complete response (CR), partial response (PR), or stable disease (SD) at 3 months, and its impact on progression‐free survival (PFS) in patients with advanced GI malignancies. Clinical and genomic data of all consecutive GI tumor samples from April, 2013 to April, 2016 sequenced by FoundationOne were obtained and analyzed. A total of 101 samples from 97 patients were analyzed. Ninety‐eight samples from 95 patients could be amplified making this approach feasible in 97% of the samples. After removing duplicates, 95 samples from 95 patients were included in the further analysis. Median time from specimen collection to reporting was 11 days. Genomic alteration‐guided treatment recommendations were considered new and clinically relevant in 38% (36/95) of the patients. Rapid decline in functional status was noted in 25% (9/36) of these patients who could therefore not receive genomic‐guided therapy. Genomic‐guided therapy was utilized in 13 patients (13.7%) and 7 patients (7.4%) experienced clinical benefit (6 PR and 1 SD). Among these seven patients, median PFS was 10 months with some ongoing durable responses. Genomic profiling‐guided therapy can lead to clinical benefit in a subset of patients with advanced GI malignancies. Attempting genomic profiling earlier in the course of treatment prior to functional decline may allow more patients to benefit from these therapies.

Correct extent of thyroidectomy is poorly predicted preoperatively by the guidelines of the American Thyroid Association for low and intermediate risk thyroid cancers

Background. Recent guidelines from the American Thyroid Association recommend thyroid lobectomy for intrathyroidal differentiated thyroid cancers <4 cm. Our aim was to examine histology from patients with cytologic results that were positive or suspicious for malignancy to assess the extent of initial thyroidectomy based on criteria from the 2015 American Thyroid Association guidelines. Methods. We studied consecutive patients who had either a positive or suspicious for malignancy cytologic diagnosis and under prior American Thyroid Association guidelines underwent initial total thyroidectomy ± lymphadenectomy. Results. Among 447 patients, high‐risk features necessitating total thyroidectomy were present in 19% (72/380) of positive and 15% (10/67) of suspicious for malignancy patients (P = .5). Intermediate‐risk features on histology were identified postoperatively in 46% (175/380) with positive and 15% (18/67) with suspicious for malignancy fine‐needle aspiration results. In multivariable analysis, preoperative factors associated with intermediate‐risk disease included age ≥45 years, women, larger tumor size, positive fine‐needle aspiration cytology, and BRAF V600E or RET/PTC positivity. Conclusion. When patients are considered for lobectomy under the 2015 American Thyroid Association guidelines, ˜ 60% with positive and 30% with suspicious for malignancy cytology would need completion thyroidectomy based on intermediate‐risk disease. The cost and risk implications of the new American Thyroid Association strategy were substantial and better tools are needed to improve preoperative risk stratification.

Postoperative narcotic use is associated with development of clinically relevant pancreatic fistulas after distal pancreatectomy

Background. Various strategies to decrease postoperative pancreatic fistula after a distal pancreatectomy have proved unsuccessful. Because narcotics can cause spasm of the sphincter of Oddi and thereby increase pressure within the pancreatic duct stump, we hypothesized that increased narcotic use would be associated with increased occurrence of clinically relevant postoperative pancreatic fistula after distal pancreatectomy. Methods. Retrospective analysis of consecutive distal pancreatectomies (2011–2016) was performed. Postoperative narcotic use was calculated in morphine equivalents. Postoperative pancreatic fistula was graded according to the International Study Group on Pancreatic Surgery. Perioperative variables were evaluated using multivariate logistic regression with clinically relevant postoperative pancreatic fistula as the dependent outcome. Results. In the study, 310 distal pancreatectomies were analyzed (61% robotic, 20% open, 19% laparoscopic). Average age was 62 (53% female), and median total dose of morphine equivalents was 424 mg (interquartile range 242–768). Clinically relevant postoperative pancreatic fistula occurred in 21.6%. Clinically relevant postoperative pancreatic fistula and not clinically relevant postoperative pancreatic fistula cohorts were similar in most demographics and operative variables, but clinically relevant postoperative pancreatic fistula patients had fewer stapled transections (80 vs 90%, P = .025), less pancreatic cancers (11 vs 35%, P < .001), and greater median total morphine equivalents (577 vs 403 mg, P < .009). On univariate analysis, clinically relevant postoperative pancreatic fistula was associated with body mass index, nonstapled transection, suture ligation of the PD, a nonpancreatic cancer pathology, prophylactic octreotide, and total morphine equivalents >424 (cohort median). On multivariate analysis, only pancreatic cancer pathology was protective against a clinically relevant postoperative pancreatic fistula (odds ratio 0.24, confidence interval, 0.10–0.50, P = .001), while increasing total morphine equivalents were predictive of a clinically relevant postoperative pancreatic fistula (odds ratio 1.13, confidence interval, 1.01–1.27, P = .035) with a 13% increased risk for every approximate ≈100 mg increase in total morphine equivalents. Conclusion. In this retrospective analysis, postoperative narcotic use was associated with the development of clinically relevant postoperative pancreatic fistula after distal pancreatectomy. Limiting narcotic use may be one of the few available mitigating strategies against the development of a clinically relevant postoperative pancreatic fistula after distal pancreatectomy.

Reply to letter: "Influence of margins on overall survival after hepatic resection for colorectal metastasis: a meta-analysis"

To the Editor: W ith great interest, we read the article by Dhir et al.1 The authors have put great effort into this meta-analysis, in which they summarized the data of 18 articles published between 1988 and 2010 on resection margins of colorectal liver metastases. They plead for a tumor-free margin of 1 cm because this was associated with a statistically significant survival benefit as compared with subcentimeter margins. If this is true, current practice, in which we try to preserve liver tissue to enable removal of either multiple metastases or bilobar liver metastases, should be changed. However, further evidence is required to support the aforementioned conclusion. First, the paradigm of the 1-cm margin is based on the occurrence of 95% of micrometastases within 1 cm of the metastasis.2 Better understanding of tumor biology of colorectal metastasis is essential. We need information on the type of recurrence. If smaller margins are not accompanied by an increase in local recurrence near the resection border as opposed to recurrences elsewhere in the liver or pulmonal metastases, the influence of these micrometastases may be limited and may not be the explanation of survival benefit. Second, the heterogeneity of the studies does not allow firm inferences. Heterogeneity may be statistical or clinical. The authors attempted to ameliorate statistical heterogeneity by using a random effects model. However, with an outlying study by Minagawa et al3 in which a smaller resection margin was in fact beneficial, heterogeneity is apparent. Clinical heterogeneity is present within the studies as they often cover data collected for over more than a decade. Liver surgery, including diagnostic workup and perioperative care of the patient, has undergone profound changes since the 1990s. Furthermore, heterogeneity between studies is present. Variables that may influence survival such as the administration of (neo)adjuvant chemotherapy differ between studies. In recently published studies by Are et al,4 Pawlik et al,5 and Muratore et al,6 chemotherapy was administered in 30% (neoadjuvant), 60% (adjuvant),