Christy Chai

A Prospective Randomized Multicenter Trial of Distal Pancreatectomy with and Without Routine Intraperitoneal Drainage

Objective: The objective of this study was to test the hypothesis that distal pancreatectomy (DP) without intraperitoneal drainage does not affect the frequency of grade 2 or higher grade complications. Background: The use of routine intraperitoneal drains during DP is controversial. Prior to this study, no prospective trial focusing on DP without intraperitoneal drainage has been reported. Methods: Patients undergoing DP for all causes at 14 high-volume pancreas centers were preoperatively randomized to placement of a drain or no drain. Complications and their severity were tracked for 60 days and mortality for 90 days. The study was powered to detect a 15% positive or negative difference in the rate of grade 2 or higher grade complications. All data were collected prospectively and source documents were reviewed at the coordinating center to confirm completeness and accuracy. Results: A total of 344 patients underwent DP with (N = 174) and without (N = 170) the use of intraperitoneal drainage. There were no differences between cohorts in demographics, comorbidities, pathology, pancreatic duct size, pancreas texture, or operative technique. There was no difference in the rate of grade 2 or higher grade complications (44% vs. 42%, P = 0.80). There was no difference in clinically relevant postoperative pancreatic fistula (18% vs 12%, P = 0.11) or mortality (0% vs 1%, P = 0.24). DP without routine intraperitoneal drainage was associated with a higher incidence of intra-abdominal fluid collection (9% vs 22%, P = 0.0004). There was no difference in the frequency of postoperative imaging, percutaneous drain placement, reoperation, readmission, or quality of life scores. Conclusions: This prospective randomized multicenter trial provides evidence that clinical outcomes are comparable in DP with or without intraperitoneal drainage.

The role of surgery and adjuvant therapy in lymph node‐positive cancers of the gallbladder and intrahepatic bile ducts

Lymph node metastasis is a poor prognostic factor for biliary tract cancers (BTCs). The optimal management of patients who have BTC with positive regional lymph nodes, including the impact of surgery and adjuvant therapy (AT), is unclear.

Management of Stage I Squamous Cell Carcinoma of the Anal Canal

Importance The incidence of squamous cell carcinoma of the anal canal (SCCAC) is increasing. Although standard management of SCCAC includes the use of concurrent chemotherapy and radiotherapy (chemoradiotherapy), data are lacking on potentially less morbid, alternative management strategies, such as local excision, among patients with node-negative T1 disease. Objectives To examine the use of local excision among patients with T1 SCCAC and to compare overall survival relative to those who received standard treatment with chemoradiotherapy. Design, Setting, and Participants This retrospective cohort study assessed 2243 patients in the National Cancer Database (2004-2012) between 18 and 80 years of age with T1N0M0 SCCAC. The association between the type of treatment received and overall risk of death was evaluated using multivariable Cox proportional hazards regression models. Data analysis was performed from June 29, 2016, to April 17, 2017. Main Outcomes and Measures Overall survival. Results Among 2243 patients with T1N0 SCCAC, 503 (22.4%) were treated with local excision alone (mean [SD] age, 54.5 [12.1] years; 240 [47.7%] male; 419 [83.3%] white) and 1740 with chemoradiotherapy (mean [SD] age, 57.0 [10.6] years; 562 [32.3%] male; 1547 [88.9%] white). Among those treated with chemoradiotherapy, 12 patients underwent a subsequent abdominoperineal resection. There was a statistically significant increase in the use of local excision during the study period (34 [17.3%] in 2004 to 68 [30.8%] in 2012; trend test, P < .001). This increase in use was observed among patients with primary tumors that measured 1 cm or smaller and greater than 1 cm to 2 cm or smaller (trend test, P < .001 for both). Overall survival at 5 years was not significantly different for the 2 management strategies (85.3% in the local excision cohort and 86.8% in the chemoradiotherapy cohort; log-rank test, P = .93). Overall risk of death was not significantly different for local excision alone relative to that for treatment with chemoradiotherapy (hazard ratio, 1.06; 95% CI, 0.78-1.44). These findings were robust when stratified by tumor size and when patients who underwent abdominoperineal resection after chemoradiotherapy were excluded. Conclusions and Relevance The use of local excision alone for the management of T1N0 SCCAC has significantly increased over time, with no clear decrement in overall survival. Because local excision may represent a lower-cost, less morbid treatment option for select patients with SCCAC, future studies are needed to better delineate its role and efficacy relative to the current standard of chemoradiotherapy.

Association of the Addition of Oral Antibiotics to Mechanical Bowel Preparation for Left Colon and Rectal Cancer Resections With Reduction of Surgical Site Infections

Importance Surgical site infections (SSIs) after colorectal surgery remain a significant complication, particularly for patients with cancer, because they can delay the administration of adjuvant therapy. A combination of oral antibiotics and mechanical bowel preparation (MBP) is a potential, yet controversial, SSI prevention strategy. Objective To determine the association of the addition of oral antibiotics to MBP with preventing SSIs in left colon and rectal cancer resections and its association with the timely administration of adjuvant therapy. Design, Setting, and Participants A retrospective review was performed of 89 patients undergoing left colon and rectal cancer resections from October 1, 2013, to December 31, 2016, at a single institution. A bowel regimen of oral antibiotics and MBP (neomycin sulfate, metronidazole hydrochloride, and magnesium citrate) was implemented August 1, 2015. Patients receiving MBP and oral antibiotics and those undergoing MBP without oral antibiotics were compared using univariate analysis. Multivariable logistic regression controlling for factors that may affect SSIs was used to evaluate the association between use of oral antibiotics and MBP and the occurrence of SSIs. Main Outcomes and Measures Surgical site infections within 30 days of the index procedure and time to adjuvant therapy. Results Of the 89 patients (5 women and 84 men; mean [SD] age, 65.3 [9.2] years) in the study, 49 underwent surgery with MBP but without oral antibiotics and 40 underwent surgery with MBP and oral antibiotics. The patients who received oral antibiotics and MBP were younger than those who received only MBP (mean [SD] age, 62.6 [9.1] vs 67.5 [8.8] years; P = .01), but these 2 cohorts of patients were otherwise similar in baseline demographic, clinical, and cancer characteristics. Surgical approach (minimally invasive vs open) and case type were similarly distributed; however, the median operative time of patients who received oral antibiotics and MBP was longer than that of patients who received MBP only (391 minutes [interquartile range, 302-550 minutes] vs 348 minutes [interquartile range, 248-425 minutes]; P = .03). The overall SSI rate was lower for patients who received oral antibiotics and MBP than for patients who received MBP only (3 [8%] vs 13 [27%]; P = .03), with no deep or organ space SSIs or anastomotic leaks in patients who received oral antibiotics and MBP compared with 9 organ space SSIs (18%; P = .004) and 5 anastomotic leaks (10%; P = .06) in patients who received MBP only. Despite this finding, there was no difference in median days to adjuvant therapy between the 2 cohorts (60 days [interquartile range, 46-73 days] for patients who received MBP only vs 72 days [interquartile range, 59-85 days] for patients who received oral antibiotics and MBP; P = .13). Oral antibiotics and MBP (odds ratio, 0.11; 95% CI, 0.02-0.86; P = .04) and minimally invasive surgery (odds ratio, 0.22; 95% CI, 0.05-0.89; P = .03) were independently associated with reduced odds of SSIs. Conclusions and Relevance The combination of oral antibiotics and MBP is associated with a significant decrease in the rate of SSIs and should be considered for patients undergoing elective left colon and rectal cancer resections.

National Quality Forum Colon Cancer Quality Metric Performance

Objective: To evaluate the impact of care at high-performing hospitals on the National Quality Forum (NQF) colon cancer metrics. Background: The NQF endorses evaluating ≥12 lymph nodes (LNs), adjuvant chemotherapy (AC) for stage III patients, and AC within 4 months of diagnosis as colon cancer quality indicators. Data on hospital-level metric performance and the association with survival are unclear. Methods: Retrospective cohort study of 218,186 patients with resected stage I to III colon cancer in the National Cancer Data Base (2004–2012). High-performing hospitals (>75% achievement) were identified by the proportion of patients achieving each measure. The association between hospital performance and survival was evaluated using Cox shared frailty modeling. Results: Only hospital LN performance improved (15.8% in 2004 vs 80.7% in 2012; trend test, P < 0.001), with 45.9% of hospitals performing well on all 3 measures concurrently in the most recent study year. Overall, 5-year survival was 75.0%, 72.3%, 72.5%, and 69.5% for those treated at hospitals with high performance on 3, 2, 1, and 0 metrics, respectively (log-rank, P < 0.001). Care at hospitals with high metric performance was associated with lower risk of death in a dose-response fashion [0 metrics, reference; 1, hazard ratio (HR) 0.96 (0.89–1.03); 2, HR 0.92 (0.87–0.98); 3, HR 0.85 (0.80–0.90); 2 vs 1, HR 0.96 (0.91–1.01); 3 vs 1, HR 0.89 (0.84–0.93); 3 vs 2, HR 0.95 (0.89–0.95)]. Performance on metrics in combination was associated with lower risk of death [LN + AC, HR 0.86 (0.78–0.95); AC + timely AC, HR 0.92 (0.87–0.98); LN + AC + timely AC, HR 0.85 (0.80–0.90)], whereas individual measures were not [LN, HR 0.95 (0.88–1.04); AC, HR 0.95 (0.87–1.05)]. Conclusions: Less than half of hospitals perform well on these NQF colon cancer metrics concurrently, and high performance on individual measures is not associated with improved survival. Quality improvement efforts should shift focus from individual measures to defining composite measures encompassing the overall multimodal care pathway and capturing successful transitions from one care modality to another.

Understaging of clinical stage I pancreatic cancer and the impact of multimodality therapy

Background: Although current guidelines recommend multimodal therapy for all patients with pancreatic ductal adenocarcinoma, it is unclear the extent to which clinical stage I patients are accurately staged and how this may affect management. Methods: In this retrospective cohort study of 4,404 patients aged 18–79 years with clinical stage 1 (ie, T1N0 or T2N0) pancreatic ductal adenocarcinoma treated with upfront resection in the National Cancer Database (2004–2014), understaging was ascertained by comparing pretreatment clinical stage with pathologic stage. The association between adjuvant treatment and overall risk of death among true stage I and understaged patients was evaluated using multivariable Cox regression. Results: Upstaging was identified in 72.6% of patients (62.8% T3/4, 53.9% N1) of whom 69.7% received adjuvant therapy compared with 47.0% with true stage I disease. Overall survival at 5 years among those with true stage I disease was significantly higher than those who had been clinically understaged (42.9% vs 16.6%; log‐rank, p < 0.001). For true stage I patients, adjuvant therapy was not associated with risk of death (hazard ratio: 1.07, 95% confidence interval: 0.89–1.29). For understaged patients, adjuvant therapy significantly decreased risk of death (hazard ratio: 0.64, 95% confidence interval: 0.55–0.74). Conclusion: The majority of clinical stage I pancreatic ductal adenocarcinoma patients actually have higher‐stage disease and benefit from multimodal therapy; however, one third of understaged patients do not receive any adjuvant treatment. Clinicians should discuss all potential treatment strategies with patients (in the context of the acknowledged risks and benefits), including the utilization of neoadjuvant approaches in those presenting with potentially resectable disease.

Value of lymph node positivity in treatment planning for early stage pancreatic cancer

Background: Multimodal therapy is recommended for early stage pancreatic cancer, although whether all patients benefit and the optimal timing of chemotherapy remain unclear. Methods: Retrospective cohort study of patients aged 18–79 years with stage I‐II pancreatic ductal adenocarcinoma in the National Cancer Database (2004–2012). Patients were grouped based on treatment strategy as surgery only, adjuvant, and preoperative. Accuracy of nodal staging and rate of nodal downstaging were ascertained using pretreatment clinical and postresection pathologic nodal status data. Association between overall risk of death and treatment strategy was evaluated with multivariable Cox regression. Results: Among 19,031 patients, 31.1% underwent surgery only, 59.6% received adjuvant, and 9.3% preoperative therapy. Based on patients receiving upfront surgery, clinical nodal staging bore sensitivity, specificity, positive predictive value, and negative predictive value of 46.2%, 95.7%, 95.1%, and 49.8%, respectively. Preoperative therapy downstaged 38% of cN1 patients to ypN0; 5‐year overall survival for this group was 27.2% vs 12.3% for ypN1 patients (P < .001). Relative to surgery only, adjuvant (HR 0.75, 95% CI [0.71–0.78]) and preoperative therapy (HR 0.66 [0.60–0.73]) were associated with lower risk of death among patients with pN1, but not pN0 (adjuvant—HR 1.01 [0.94–1.09]; preoperative—HR 1.10 [0.99–1.22]), disease. Conclusion: Our data provide strong support for preoperative chemotherapy for patients with node‐positive pancreatic cancer, one third of whom may be downstaged. Among those with seemingly node‐negative disease, half will be understaged with current clinical staging modalities. These results should be considered when planning treatment for patients with early stage pancreatic cancer.

Pre-SN Ultrasound-FNAC for Lymph Node Metastases in Melanoma Patients: A Reply

We thank Drs. Voit, van Akkooi, Catalano, and Eggermont—unquestioned pioneers in this field—for their interest in our paper, and we are pleased to have the opportunity to address several key points mentioned in their letter. We believe that our conclusions are sound and neither premature nor misleading. Specifically, we concluded that ‘‘preoperative ultrasound without lymphoscintigraphic localization will provide incomplete evaluation in many cases.’’ So, we agree that targeting ultrasound with lymphoscintigraphy might increase the sensitivity of ultrasound. However, as we discussed and others have found, targeted ultrasound does not necessarily guarantee improved sensitivity. Furthermore, there are major practical hurdles involved in obtaining lymphoscintigraphy plus ultrasonography, with or without fine needle aspiration cytology (FNAC), and performing a sentinel lymph node biopsy (SLNB) the same or the following day with a definitive FNAC report available for the surgeon. This approach is not feasible in our Comprehensive Cancer Center, where we see nearly 2000 new patients with cutaneous malignancies per year, and we believe that it is neither feasible nor cost-effective for most hospitals in the United States or abroad. Hence, we stand by our conclusion that ‘‘routine preoperative ultrasound in clinically node-negative melanoma is impractical because of its low sensitivity.’’ Importantly, this conclusion is identical to that of Thompson et al., who found that the sensitivity of ultrasound was only 8% based on an interim analysis of the prospective MSLT-II clinical trial. The MSLT-II protocol was amended so that preoperative ultrasound is no longer performed for patients entering the trial. Voit et al. voiced their disappointment that we did not utilize their ultrasound morphology criteria, although these specific criteria were not published until 2010, 1 year after our last patient was evaluated. In fact, even today, there are no uniformly accepted criteria for sonographic lymph node evaluation in the literature. A recent systematic review concluded that the diagnostic criteria used in the literature to diagnose lymph node malignancy with ultrasound were frequently vague and contradictory and emphasized the need for validating proposed criteria in large series with histologic confirmation. Even though Voit et al. published a 65% detection rate of sentinel node metastases using targeted ultrasound-guided FNAC (86% for metastases [ 1 mm in greatest dimension, 46% for metastases 0.1–1 mm, and 23% in for metastases \ 0.1 mm) using their morphology criteria, these results have as yet neither been reproduced nor validated. Previous publications from Voit’s group acknowledged the singleinstitution nature of their studies and stated that the peripheral perfusion criterion needs further validation as an early sign of nodal metastasis in multicenter prospective trials, which we heartily support. Finally, while Voit et al. mention the ability to identify metastases as small as 0.4 mm in their letter, the current limits of reliable detection in most hands are more like 4–6 mm. Most nodal metastases diagnosed today are far smaller than this. In the interim analysis of MSLT-II previously cited, sentinel node metastases found by ultrasound had a median cross-sectional area of 6.11 mm, whereas the median cross-sectional area of metastases with negative ultrasounds was 0.16 mm. Although the size of the nodal Society of Surgical Oncology 2017