Michael L. Kendrick

In Brief Objective: To directly compare the oncologic outcomes of TLPD and OPD in the setting of pancreatic ductal adenocarcinoma. Background: Total laparoscopic pancreaticoduodenectomy (TLPD) has been demonstrated to be feasible and may have several potential advantages over open pancreaticoduodenectomy (OPD), including lower blood loss and shorter hospital stay. Whether potential advantages could allow patients to recover in a timelier manner and pursue adjuvant treatment options remains to be answered. Methods: We reviewed data for all patients undergoing TLPD (N = 108) or OPD (N = 214) for pancreatic ductal adenocarcinoma at our institution between January 2008 and July 2013. Results: Neoadjuvant therapy, tumor size, node positivity, and margin-positive resection were not significantly different between the 2 groups. Median length of hospital stay was significantly longer in the OPD group (9 days; range, 5–73 days) than in the TLPD group (6 days; range, 4–118 days; P < 0.001). There was a significantly higher proportion of patients in the OPD group (12%) who had a delay of greater than 90 days or who did not receive adjuvant chemotherapy at all compared with that in the TLPD group (5%; P = 0.04). There was no significant difference in overall survival between the 2 groups (P = 0.22). A significantly longer progression-free survival was seen in the TLPD group than in the OPD group (P = 0.03). Conclusions: TLPD is not only feasible in the setting of pancreatic ductal adenocarcinoma but also has advantages such as shorter hospital stay and faster recovery, allowing patients to recover in a timelier manner and pursue adjuvant treatment options. This study also demonstrated a longer progression-free survival in patients undergoing TLPD than those undergoing OPD. The oncologic outcomes of total laparoscopic pancreaticoduodenenctomy (TLPD) and open pancreaticoduodenectomy (OPD) in the treatment of pancreatic ductal adenocarcinoma were compared. There was a lower proportion of patients in the TLPD group (5%) who had a delay of greater than 90 days or who did not receive adjuvant chemotherapy compared with that in the OPD group (12%).

OBJECTIVE: To identify predictive factors associated with operative morbidity, mortality, and survival outcomes in patients with borderline resectable (BR) or locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC) undergoing total neoadjuvant therapy (TNT). BACKGROUND: The optimal preoperative treatment sequencing for BR/LA PDA is unknown. TNT, or systemic chemotherapy followed by chemoradiation (CRT), addresses both occult metastases and positive margin risks and thus is a potentially optimal strategy; however, factors predictive of perioperative and survival outcomes are currently undefined. METHODS: We reviewed our experience in BR/LA patients undergoing resection from 2010 to 2017 following TNT assessing operative morbidity, mortality, and survival in order to define outcome predictors and response endpoints. RESULTS: One hundred ninety-four patients underwent resection after TNT, including 123 (63%) BR and 71 (37%) LA PDAC. FOLFIRINOX or gemcitabine along with nab-paclitaxel were used in 165 (85%) and 65 (34%) patients, with 36 (19%) requiring chemotherapeutic switch before long-course CRT and subsequent resection. Radiologic anatomical downstaging was uncommon (28%). En bloc venous and/or arterial resection was required in 125 (65%) patients with 94% of patients achieving R0 margins. The 90-day major morbidity and mortality was 36% and 6.7%, respectively. Excluding operative mortalities, the median, 1-year, 2-year, and 3-year recurrence-free survival (RFS) [overall survival (OS)] rates were 23.5 (58.8) months, 65 (96)%, 48 (78)%, and 32 (62)%, respectively. Radiologic downstaging, vascular resection, and chemotherapy regimen/switch were not associated with survival. Only 3 factors independently associated with prolonged survival, including extended duration (≥6 cycles) chemotherapy, optimal post-chemotherapy CA19-9 response, and major pathologic response. Patients achieving all 3 factors had superior survival outcomes with a survival detriment for each failing factor. In a subset of patients with interval metabolic (PET) imaging after initial chemotherapy, complete metabolic response highly correlated with major pathologic response. CONCLUSION: Our TNT experience in resected BR/LA PDAC revealed high negative margin rates despite low radiologic downstaging. Extended duration chemotherapy with associated biochemical and pathologic responses highly predicted postoperative survival. Potential modifications of initial chemotherapy treatment include extending cycle duration to normalize CA19-9 or achieve complete metabolic response, or consideration of chemotherapeutic switch in order to achieve these factors may improve survival before moving forward with CRT and subsequent resection.

Populations of interstitial cells of Cajal (ICC) are altered in several gastrointestinal neuromuscular disorders. ICC are identified typically by ultrastructure and expression of Kit (CD117), a protein that is also expressed on mast cells. No other molecular marker currently exists to independently identify ICC. The expression of ANO1 (DOG1, TMEM16A), a Ca(2+)-activated Cl(-) channel, in gastrointestinal stromal tumors suggests it may be useful as an ICC marker. The aims of this study were therefore to determine the distribution of Ano1 immunoreactivity compared with Kit and to establish whether Ano1 is a reliable marker for human and mouse ICC. Expression of Ano1 in human and mouse stomach, small intestine, and colon was investigated by immunofluorescence labeling using antibodies to Ano1 alone and in combination with antibodies to Kit. Colocalization of immunoreactivity was demonstrated by epifluorescence and confocal microscopy. In the muscularis propria, Ano1 immunoreactivity was restricted to cells with the morphology and distribution of ICC. All Ano1-positive cells in the muscularis propria were also Kit positive. Kit-expressing mast cells were not Ano1 positive. Some non-ICC in the mucosa and submucosa of human tissues were Ano1 positive but Kit negative. A few (3.2%) Ano1-positive cells in the human gastric muscularis propria were labeled weakly for Kit. Ano1 labels all classes of ICC and represents a highly specific marker for studying the distribution of ICC in mouse and human tissues with an advantage over Kit since it does not label mast cells.

HYPOTHESIS: Total laparoscopic pancreaticoduodenectomy is a safe and effective therapeutic approach. DESIGN: Single-institutional retrospective review. SETTING: Tertiary referral center. PATIENTS: All consecutive patients undergoing total laparoscopic pancreaticoduodenectomy from July 2007 through July 2009 at a single center (n = 62). MAIN OUTCOME MEASURES: Blood loss, operative time, postoperative morbidity, length of hospital stay, and 30-day or in-hospital mortality. RESULTS: Of 65 patients undergoing laparoscopic resection, 62 patients with a mean age of 66 years (SD, 12 years) underwent total laparoscopic pancreaticoduodenectomy. The pancreaticojejunostomy consisted of a duct-to-mucosa anastomosis with interrupted suture. Median operative time was 368 minutes (range, 258-608 minutes) and median blood loss was 240 mL (range, 30-1200 mL). Diagnosis was pancreatic adenocarcinoma (n = 31), intraductal papillary mucinous neoplasm (n = 12), periampullary adenocarcinoma (n = 8), neuroendocrine tumor (n = 4), chronic pancreatitis (n = 3), cholangiocarcinoma (n = 1), metastatic renal cell carcinoma (n = 1), cystadenoma (n = 1), and duodenal adenoma (n = 1). Median tumor size was 3 cm (range, 0.9-10.0 cm) and the median number of lymph nodes harvested was 15 (range, 6-31). Perioperative morbidity occurred in 26 patients and included pancreatic fistula (n = 11), delayed gastric emptying (n = 9), bleeding (n = 5), and deep vein thrombosis (n = 2). There was 1 postoperative mortality. Median length of hospital stay was 7 days (range, 4-69 days). CONCLUSIONS: Laparoscopic pancreaticoduodenectomy is feasible, safe, and effective. Outcomes appear comparable with those via the open approach; however, controlled trials are needed. Despite this series representing experience within the learning curve, laparoscopic pancreaticoduodenectomy holds promise for providing advantages seen with minimally invasive approaches in other procedures.

BACKGROUND: Anastomotic leaks are a dreaded complication of bariatric surgery. The objective of this study was to describe the clinical presentation and outcomes of treatment in patients who develop anastomotic leaks after Roux-en-Y gastric bypass for obesity. STUDY DESIGN: Prospectively collected data on 3,018 consecutive patients who underwent Roux-en-Y gastric bypass in 4 tertiary referral centers were reviewed. RESULTS: Sixty-three patients (2.1%) developed anastomotic leaks (open, 2.1%; laparoscopic, 2.1%) at a median of 3 days (range 0 to 28 days) after Roux-en-Y gastric bypass. Symptoms and signs included tachycardia (72%), fever (63%), or abdominal pain (54%). Upper gastrointestinal series and CT demonstrated leaks in only 17 of 56 (30%) and 28 of 50 (56%) patients, respectively; when done jointly, both studies were negative in 30% of patients. The 68 anastomotic leaks occurred at the gastrojejunostomy (49%), excluded stomach (25%), jejunojejunostomy (13%), gastric pouch (9%), and uncertain location (4%). Forty patients (63%) required 58 reoperations for drainage of intraabdominal collections (55%), repair of anastomotic defects (34%), or revision of the leaking anastomosis (11%), with an overall morbidity of 53% and mortality of 10%. Nonoperative treatment was successful in 23 of 26 patients, with an overall morbidity of 61% and no mortality (p=NS versus operative). Operative treatment was more common in patients with hypotension or oliguria (p < 0.01). CONCLUSIONS: Lack of specificity in clinical presentation and imaging studies make diagnosing anastomotic leaks challenging, so operative exploration should be part of the diagnostic algorithm. Nonoperative treatment is safe and effective in a subset of patients who exhibit stable hemodynamic parameters and are known to have controlled leaks.