Opioid analgesia in necrotizing pancreatitis: Incidence and timing of a hidden crisis.

BACKGROUND: Rates of opioid usage during necrotizing pancreatitis (NP) disease course are unknown. We hypothesized that a significant number of NP patients were prescribed opioid analgesics chronically. METHODS: Single institution IRB-approved retrospective study of 230 NP patients treated between 2015 and 2019. RESULTS: Data were available for 198/230 (86%) patients. 166/198 (84%) were discharged from their index hospitalization with a prescription for an opioid. At the first clinic visit following hospitalization, 110/182 (60%) were using opioids. Six months after disease onset, 72/163 (44%) continued to require opioids. At disease resolution, 38/144 (26%) patients remained on opioid medications. The rate of active opioid prescriptions at six months after disease onset declined throughout the period studied from 68% in 2015 to 39% in 2019. CONCLUSIONS: Opioid prescriptions are common in NP. Despite decline over time, 1 in 4 patients remain on opioids at disease resolution. These data identify an opportunity to adjust analgesic prescription practice in NP patients.

Routine Gastric Decompression after Pancreatoduodenectomy: Treating the Surgeon?

BACKGROUND: The decision to routinely leave a nasogastric tube after pancreatoduodenectomy remains controversial. We sought to determine the impact of immediate nasogastric tube removal versus early nasogastric tube removal (<24 h) on postoperative outcomes. METHODS: A retrospective review of our institution's prospective ACS-NSQIP database identified patients that underwent pancreatoduodenectomy from 2015 to 2018. Outcomes were compared among patients with immediate nasogastric tube removal versus early nasogastric tube removal. RESULTS: A total of 365 patients were included in primary analysis (no nasogastric tube, n = 99; nasogastric tube removed <24 h, n = 266). Thirty-day mortality and infectious, renal, cardiovascular, and pulmonary morbidity were similar in comparing those with no nasogastric tube versus early nasogastric tube removal on univariable and multivariable analyses (P > 0.05). Incidence of delayed gastric emptying (11.1 versus 13.2%) was similar between groups. Patients with no nasogastric tube less frequently required nasogastric tube reinsertion (n = 4, 4%) compared to patients with NGT <24 h (n = 39, 15%) (OR = 3.83, 95% CI [1.39-10.58]; P = 0.009). CONCLUSION: Routine gastric decompression can be safely avoided after uneventful pancreaticoduodenectomy.

Necrotizing Pancreatitis from Hypertriglyceridemia: More Severe Disease?

BACKGROUND: Necrotizing pancreatitis (NP) is caused by hypertriglyceridemia (HTG) in up to 10% of patients. Clinical experience suggests that HTG-NP is associated with increased clinical severity; objective evidence is limited and has not been specifically studied in NP. AIM: The aim of this study was to critically evaluate outcomes in HTG-NP. We hypothesized that patients with HTG-NP had significantly increased severity, morbidity, and mortality compared to patients with NP from other etiologies. METHODS: A case-control study of all NP patients treated at a single institution between 2005 and 2018 was performed. Diagnostic criteria of HTG-NP included a serum triglyceride level > 1000 mg/dL and the absence of another specific pancreatitis etiology. To control for differences in age, sex, and comorbidities, non-HTG and HTG patients were matched at a 4:1 ratio using propensity scores. Outcomes were compared between non-HTG and HTG patients. RESULTS: A total of 676 NP patients were treated during the study period. The incidence of HTG-NP was 5.8% (n = 39). The mean peak triglyceride level at diagnosis was 2923 mg/dL (SEM, 417 mg/dL). After propensity matching, no differences were found between non-HTG and HTG patients in CT severity index, degree of glandular necrosis, organ failure, infected necrosis, necrosis intervention, index admission LOS, readmission, total hospital LOS, or disease duration (P = NS). Mortality was similar in non-HTG-NP (7.1%) and HTG-NP (7.7%), P = 1.0. CONCLUSION: In this large, single-institution series, necrotizing pancreatitis caused by hypertriglyceridemia had similar disease severity, morbidity, and mortality as necrotizing pancreatitis caused by other etiologies.

Hepatic Steatosis After Neoadjuvant Chemotherapy for Pancreatic Cancer: Incidence and Implications for Outcomes After Pancreatoduodenectomy.

BACKGROUND: This study aimed to determine the incidence of new onset hepatic steatosis after neoadjuvant chemotherapy for pancreatic cancer and its impact on outcomes after pancreatoduodenectomy. METHODS: Retrospective review identified patients who received neoadjuvant chemotherapy for pancreatic adenocarcinoma and underwent pancreatoduodenectomy from 2013 to 2018. Preoperative computed tomography scans were evaluated for the development of hepatic steatosis after neoadjuvant chemotherapy. Hypoattenuation included liver attenuation greater than or equal to 10 Hounsfield units less than tissue density of spleen on noncontrast computed tomography and greater than or equal to 20 Hounsfield units less on contrast-enhanced computed tomography. RESULTS: One hundred forty-nine patients received neoadjuvant chemotherapy for a median of 5 cycles (interquartile range (IQR), 4-6). FOLFIRINOX was the regimen in 78% of patients. Hepatic steatosis developed in 36 (24%) patients. The median time from neoadjuvant chemotherapy completion to pancreatoduodenectomy was 40 days (IQR, 29-51). Preoperative biliary stenting was performed in 126 (86%) patients. Neoadjuvant radiotherapy was delivered to 23 (15%) patients. Female gender, obesity, and prolonged exposure to chemotherapy were identified as risk factors for chemotherapy-associated hepatic steatosis. Compared with control patients without neoadjuvant chemotherapy-associated hepatic steatosis, patients developing steatosis had similar rates of postoperative pancreatic fistula (8% (control) vs. 4%, p = 0.3), delayed gastric emptying (8% vs. 14%, p = 0.4), and major morbidity (11% vs. 15%, p = 0.6). Ninety-day mortality was similar between groups (8% vs. 2%, p = 0.08). CONCLUSION: Hepatic steatosis developed in 24% of patients who received neoadjuvant chemotherapy but was not associated with increased morbidity or mortality after pancreatoduodenectomy.

Comparison of skin closure techniques in patients undergoing open pancreaticoduodenectomy: A single center experience.

BACKGROUND: This study evaluated closure techniques and incisional surgical site complications (SSCs) and incisional surgical site infections (SSIs) after pancreaticoduodenectomy (PD). METHODS: Retrospective review of open PDs from 2015 to 2018 was performed. Outcomes were compared among closure techniques (subcuticular + topical skin adhesive (TSA); staples; subcuticular only). SSCs were defined as abscess, cellulitis, seroma, or fat necrosis. SSIs were defined according to the National Surgical Quality Improvement Program (NSQIP). RESULTS: Patients with subcuticular + TSA (n = 205) were less likely to develop an incisional SSC (9.8%) compared to staples (n = 139) (20.1%) and subcuticular (n = 74) (16.2%) on univariable analysis (P = 0.024). Multivariable analysis revealed no statistically significant difference in incisional SSC between subcuticular + TSA and subcuticular (P = 0.528); a significant difference remained between subcuticular + TSA and staples (P = 0.014). Unadjusted median length of stay (LOS) (days) was significantly longer for staples (9) vs. subcuticular (8) vs. subcuticular + TSA (7); P < 0.001. Incisional SSIs were evaluated separately according to the NSQIP definition. When comparing rates, the subcuticular + TSA group experienced lower incisional SSIs compared to the other two techniques (4.9% vs. 10.1%, 10.8%). However, this difference was not statistically significant by either univariable or multivariable analysis. CONCLUSIONS: Subcuticular suture + TSA reduces the risk of incisional SSCs when compared to staples alone after pancreaticoduodenectomy.

Smoking and IPMN malignant progression.

BACKGROUND: Patients with intraductal papillary mucinous neoplasm (IPMN) are at risk for invasive pancreatic cancer. We aim to characterize the impact of smoking on IPMN malignant progression. METHODS: Patients undergoing pancreatic resection for IPMN (1991-2015) were retrospectively reviewed using a prospectively collected database. RESULTS: Of 422 patients identified, 324 had complete data for analysis; 55% were smokers. Smoking status did not impact IPMN malignant progression (smokers/non-smokers: 22%/18% invasive grade; p = 0.5). Smokers were younger than non-smokers at the time of IPMN diagnosis (63 versus 68 years; p = 0.001). This association also held in the invasive IPMN subgroup (65 versus 72 years, p = 0.01). Despite this observation, rate of symptoms at diagnosis, cancer stage, and median survival were the same between smokers and non-smokers. CONCLUSION: Although smoking is not associated with IPMN malignant progression, invasive IPMN is diagnosed at a younger age in smokers. These data suggest tobacco exposure may accelerate IPMN malignant progression.

Does preoperative cross-sectional imaging accurately predict main duct involvement in intraductal papillary mucinous neoplasm?

Main pancreatic duct (MPD) involvement is a well-demonstrated risk factor for malignancy in intraductal papillary mucinous neoplasm (IPMN). Preoperative radiographic determination of IPMN type is heavily relied upon in oncologic risk stratification. We hypothesized that radiographic assessment of MPD involvement in IPMN is an accurate predictor of pathological MPD involvement. Data regarding all patients undergoing resection for IPMN at a single academic institution between 1992 and 2012 were gathered prospectively. Retrospective analysis of imaging and pathologic data was undertaken. Preoperative classification of IPMN type was based on cross-sectional imaging (MRI/magnetic resonance cholangiopancreatography (MRCP) and/or CT). Three hundred sixty-two patients underwent resection for IPMN. Of these, 334 had complete data for analysis. Of 164 suspected branch duct (BD) IPMN, 34 (20.7%) demonstrated MPD involvement on final pathology. Of 170 patients with suspicion of MPD involvement, 50 (29.4%) demonstrated no MPD involvement. Of 34 patients with suspected BD-IPMN who were found to have MPD involvement on pathology, 10 (29.4%) had invasive carcinoma. Alternatively, 2/50 (4%) of the patients with suspected MPD involvement who ultimately had isolated BD-IPMN demonstrated invasive carcinoma. Preoperative radiographic IPMN type did not correlate with final pathology in 25% of the patients. In addition, risk of invasive carcinoma correlates with pathologic presence of MPD involvement.

Pancreatic enucleation: improved outcomes compared to resection.

INTRODUCTION: Pancreatic enucleation is associated with a low operative mortality and preserved pancreatic parenchyma. However, enucleation is an uncommon operation, and good comparative data with resection are lacking. Therefore, the aim of this analysis was to compare the outcomes of pancreatic enucleation and resection. MATERIAL AND METHODS: From 1998 through 2010, 45 consecutive patients with small (mean, 2.3 cm) pancreatic lesions underwent enucleation. These patients were matched with 90 patients undergoing pancreatoduodenectomy (n = 38) or distal pancreatectomy (n = 52). Serious morbidity was defined in accordance with the American College of Surgeons-National Surgical Quality Improvement Program. Outcomes were compared with standard statistical analyses. RESULTS: Operative time was shorter (183 vs. 271 min, p < 0.01), and operative blood loss was significantly lower (160 vs. 691 ml, p < 0.01) with enucleation. Fewer patients undergoing enucleation required monitoring in an intensive care unit (20% vs. 41%, p < 0.02). Serious morbidity was less common among patients who underwent enucleation compared to those who had a resection (13% vs. 29%, p = 0.05). Pancreatic endocrine (4% vs. 17%, p = 0.05) and exocrine (2% vs. 17%, p < 0.05) insufficiency were less common with enucleation. Ten-year survival was no different between enucleation and resection. CONCLUSION: Compared to resection, pancreatic enucleation is associated with improved operative as well as short- and long-term postoperative outcomes. For small benign and premalignant pancreatic lesions, enucleation should be considered the procedure of choice when technically appropriate.

Very high serum CA 19-9 levels: a contraindication to pancreaticoduodenectomy?

AIM: To assess the outcome of patients with resectable pancreatic adenocarcinoma (PA) associated with high serum CA 19-9 levels. METHODS: From 2000 to 2007, 344 patients underwent pancreatoduodenectomy for PA. Fifty-three patients (elevated group) had preoperatively elevated serum CA 19-9 levels (>400 IU/ml) after resolution of obstructive jaundice. Of these, 27 patients had high levels (400-899 IU/ml (HL)) and 26 patients had very high levels >or=900 IU/ml (VHL). Fifty patients with normal preoperative serum CA 19-9 levels (<37 IU/ml) comprised the control group. RESULTS: Median survival of the control group (n = 50) versus elevated group (n = 53) was 22 versus 15 months (p = 0.02) and overall 3-year survival was 32% versus 14% (p = 0.03). There was no statistical difference in the median and 3-year overall survival between patients with HL and VHL. Patients in the elevated group who normalized their CA 19-9 levels after surgery (n = 11) had a survival equivalent to patients in the control group. CONCLUSIONS: Patients who normalized their CA19-9 levels postoperatively had equivalent survival to patients with normal preoperative CA 19-9 levels. Preoperative serum CA 19-9 level by itself should not preclude surgery in patients who have undergone careful preoperative staging.

Mechanism mediating nitric oxide-induced inhibition in human jejunal longitudinal smooth muscle.

BACKGROUND: Enteric neurotransmission is a complex process involving multiple neurotransmitters, including nitric oxide (NO). Our aim was to evaluate the role and mechanism(s) of action of NO in normal human jejunal longitudinal smooth muscle. METHODS: Transmural strips of normal human jejunum obtained from subjects undergoing gastric bypass were studied in organ chambers. Effects of exogenous NO (7 x 10(-6) mol/L to 7 x 10(-5) mol/L) and electrical field stimulation (nonspecific release of endogenous neurotransmitters) on spontaneous contractile activity and on precontracted muscle strips (substance P, 10(-5) mol/L) were evaluated in the presence and absence of the competitive NO synthase inhibitor N(G)-amino-L-arginine (L-NNA, 10(-3) mol/L) and the specific soluble guanylyl cyclase inhibitor 1H-[1,2,4]-oxadiazaolo-[4,3-a]-quinoxalin-1-one (ODQ, 10(-5) mol/L and 10(-4) mol/L). RESULTS: Exogenous NO dose-dependently inhibited spontaneous contractility and relaxed precontracted smooth muscle strips. The effects of NO were markedly attenuated or completely inhibited in the presence of ODQ. Electric field stimulation under nonadrenergic, noncholinergic conditions also inhibited spontaneous contractility and relaxed precontracted smooth muscle strips; both of these effects were attenuated, but not completely inhibited, in the presence of both ODQ and L-NNA. CONCLUSIONS: NO is an endogenous inhibitory neurotransmitter in human jejunal longitudinal smooth muscle, acting at least in part via a mechanism mediated by guanylyl cyclase. Other (non-nitrergic) nonadrenergic, noncholinergic inhibitory neurotransmitters are likely active in this portion of the human gut.

Vagal innervation modulates motor pattern but not initiation of canine gastric migrating motor complex.

To determine the role of vagal nerves in initiation and modulation of the gastric migrating motor complex (MMC), motor activity was recorded in four dogs before and after total abdominal vagotomy during fasting, after exogenous intravenous motilin and insulin, and after feeding. After vagotomy, a temporally coordinated cyclic gastric and small bowel MMC persisted with an unchanged period. During gastric phase III, vagotomy decreased number of contractions (42 +/- 4 vs. 16 +/- 2), number of groupings of contractions (14 +/- 1 vs. 7 +/- 1), and motility index (12 +/- 1 vs. 10 +/- 1) and increased the duration between groupings (1 +/- 1 vs. 3 +/- 1 min) (P < 0.05 in each). Before and after vagotomy, motilin and insulin induced a premature MMC with minor changes in contractile pattern. A 200-g liver meal but not a 50-g liver meal inhibited the gastric MMC after vagotomy. A cyclic MMC persisted after vagotomy, but the contractile pattern during gastric phase III was altered. After a short recovery period, vagal innervation to the stomach modulates the pattern but not the presence of gastric interdigestive motility during phase III.

Extrinsic neural innervation mediates absorption of water and electrolytes in canine proximal colon in vivo.

INTRODUCTION: Extrinsic innervation mediates a proabsorptive effect in small intestine. Our aim was to determine whether extrinsic neural input modulates similar effects in the proximal colon in vivo. METHODS: Ten adult dogs underwent enteric isolation of a 50-cm proximal colon loop; five each were randomized to undergo extrinsic denervation (Ext Den) of the isolated colonic segment or to serve as neurally innervated controls. After recovery, a 38 degrees C electrolyte solution (Na(+) 125 meq/L, K(+) 9 meq/L, Cl(-) 75 meq/L, HC03(-) 65 meq/L) was infused at 4 ml/min into the segment. Effluent was collected in 30-min intervals for 2 h after achieving steady state (determined by 14C nonabsorbable marker recovery); four studies were conducted at 1 and 12 weeks postoperatively. Net flux of H20, Na(+), K(+), and Cl(-) was determined. Colon morphometry was evaluated at 0 and 14 weeks. Data are presented as mean +/- SEM. Unpaired t test was applied for comparisons. RESULTS: Net absorptive flux of H20 (microL/min/cm) was decreased in Ext Den vs controls at 1 week (4.40 +/- 0.63 vs 7.92 +/- 0.92, P = 0.03) but was not different at 12 weeks (4.70 +/- 1.20 vs 5.97 +/- 0.69; P > 0.05). Na(+) and Cl(-) followed the trends in H20 absorption (P < or = 0.05). Crypt depth (microm) decreased in controls at 14 weeks vs 0 week (915 +/- 20 vs 740 +/- 07, P = 0.01) but remained unchanged in Ext Den. CONCLUSIONS: Loss of extrinsic neural input decreases colonic absorption. This observation suggests that extrinsic neural innervation provides net proabsorptive mechanisms for absorption of water and electrolytes in the proximal canine colon.

Duodenal carcinoid tumors: how aggressive should we be?

Duodenal carcinoid tumors are uncommon. It is not known whether they behave more like carcinoid tumors in the appendix (indolent course) or those in the ileum (often virulent)-crucial information for determining the need for radical resection. A retrospective review at our tertiary referral center (from 1976 to 1999) identified 27 patients with primary duodenal carcinoid lesions, excluding functional islet cell tumors. Endoscopic biopsy provided the diagnosis in 78% of patients. Treatment was by endoscopic excision (n = 11), transduodenal excision (n = 8), pancreaticoduodenectomy (n = 3), segmental distal duodenectomy (n = 2), or palliative operation (n = 2). One patient did not undergo operation because of comorbidity. Eighteen of 19 patients with tumors smaller than 2 cm remained disease free after local (endoscopic or transduodenal) excision. The exception was a patient with a small periampullary carcinoid lesion. In contrast, all four patients with carcinoid tumors 2 cm or larger who were resected for cure developed a recurrence (2 to 9 years postoperatively). We conclude that duodenal carcinoid tumors smaller than 2 cm may be excised locally; to ensure complete resection we recommend open transduodenal excision for tumors between 1 and 2 cm. Endoscopic follow-up is indicated. It is unclear whether patients with larger tumors benefit from more aggressive locoregional resection. Ampullary/periampullary carcinoid tumors should be considered separately, as their behavior is unpredictable.