A Novel Risk Score to Predict Hungry Bone Syndrome After Parathyroidectomy for Renal Hyperparathyroidism.

OBJECTIVE: Hungry bone syndrome (HBS) is a known complication of parathyroidectomy. Patients with renal hyperparathyroidism are particularly vulnerable to HBS because of their prolonged exposure to electrolyte abnormalities and elevated parathyroid hormone (PTH). However, in-depth characterization of predictive factors for HBS in these patients is lacking. METHODS: A retrospective analysis was performed of patients with renal hyperparathyroidism who underwent parathyroidectomy at a single institution from 2011-2021. Patient demographics, clinical characteristics, and biochemical data were collected and analyzed. Boruta and binary logistic regression analyses were used to develop a scoring system. RESULTS: Thirty-three patients were identified; 16 (48%) developed HBS. Patients with HBS had significantly higher preoperative levels of serum PTH (mean difference [MS] = 2167.2 pg/mL, P <.001), phosphorus (MD = 3.5 mg/dl, P <.001), and alkaline phosphatase (ALP) (MD = 344.2 U/L, P =.002) and significantly lower levels of preoperative serum calcium (MD = -0.96 mg/dL, P =.004). Stepwise regression analysis identified elevated ALP (>150 U/L) and markedly elevated PTH (>1000 pg/mL) as positive predictors of HBS. A two-point scoring system with these 2 variables had overall diagnostic accuracy of 96.8% (sensitivity 100% and specificity 94.1%) with 1 point conferring 93.8% positive predictive value and 2 points conferring 100% positive predictive value. CONCLUSION: Preoperative serum PTH and ALP are significantly associated with HBS in patients with renal hyperparathyroidism undergoing parathyroidectomy for renal hyperparathyroidism. A scoring system with these 2 variables may be of clinical utility in predicting patients at high risk of HBS.

Improving fine needle aspiration to predict the tumor biological aggressiveness in pancreatic neuroendocrine tumors using Ki-67 proliferation index, phosphorylated histone H3 (PHH3), and BCL-2.

INTRODUCTION: Surgery is the only known cure for sporadic pancreatic neuroendocrine tumors (PNETs). Therefore, the prediction of the PNETs biological aggressiveness evaluated on endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has a significant impact on clinical management. The proliferation rate of Ki-67 in PNETs can help to predict the biological aggressiveness of the tumor. In addition, there is a relatively new proliferation marker called phosphorylated histone H3 (PHH3) that can identify and quantify dividing cells in tissue samples, which is a marker highly specific to mitotic figures. Other markers such as BCL-2 also contribute to tumorigenesis and may be involved in the differentiation of neuroendocrine cells. MATERIALS AND METHODS: A retrospective observational study was performed on patients undergoing surveillance for PNETs from January 2010 to May 2021. Data collection included the patients' age, sex, tumor location, tumor size in the surgical specimen, and tumor grade in FNA. The 2019 World Health Organization (WHO) classification guideline was followed to diagnose PNETs, including grade and stage. Immunohistochemical stainings for Ki-67, PHH3 and BCL-2 in PNETs were performed. RESULTS: After excluding cell blocks containing fewer than 100 tumor cells, 44 patients with EUS-FNA and surgical resection specimens were included in this study. There were 19 cases of G1 PNETs, 20 cases of G2 PNETs, and 5 cases of G3 PNETs. The grade assigned based on the Ki-67 index was higher and more sensitive than that based on the mitotic count using H&E slides in some cases of G2 and G3 PNETs. However, there was no significant difference between the mitotic count using PHH3-positive tumor cells and the Ki-67 index to grade PNETs. All grade 1 tumors (19 cases) on surgical resection specimens were correctly graded on FNA (100 % concordance rate). Within the 20 G2 PNETs, 15 cases of grade 2 on surgical resection specimens were graded correctly on FNA based on the Ki-67 index only. Five cases of grade 2 PNETs on surgical resection specimens were graded as grade 1 on FNA when using only the Ki-67 index. Three of five grade 3 tumors on surgical resection specimens were graded as grade 2 on FNA based on the Ki-67 index only. Using only FNA Ki-67 to predict PNET tumor grade, the concordance (accuracy) rate was 81.8 % in total. However, all these eight cases (5 cases of G2 PNETs and 3 cases of G3 PNETs) were graded correctly by using the Ki-67 index plus mitotic rate (using PHH3 IHC stains). Four of 18 (22.2 %) patients with PNETs were positive for BCL-2 stain. In these 4 cases positive for BCL-2 stains, 3 cases were G2 PNETs and one case was G3 PNETs. CONCLUSION: Grade and the proliferative rate in EUS-FNA can be used to predict the tumor grade in surgical resection specimens. However, when using only FNA Ki-67 to predict PNET tumor grade, about 18 % of cases were downgraded by one level. To solve the problem, immunohistochemical staining for BCL-2 and especially PHH3 would be helpful. Our results demonstrated that the mitotic count using PHH3 IHC stains not only improved the accuracy and precision of PNET grading in the surgical resection specimens, but also could reliably be used in routine scoring of mitotic figures of FNA specimens.

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.

Neoadjuvant gemcitabine, docetaxel, and capecitabine followed by gemcitabine and capecitabine/radiation therapy and surgery in locally advanced, unresectable pancreatic adenocarcinoma.

BACKGROUND: This prospective study was undertaken to assess toxicity, resectability, and survival in pancreatic adenocarcinoma patients presenting with locally advanced, unresectable disease treated with neoadjuvant gemcitabine, docetaxel, and capecitabine (GTX) and gemcitabine and capecitabine (GX)/radiation therapy (RT). METHODS: All patients presenting to the Pancreas Center were evaluated for eligibility. Forty-five patients (mean age, 64 years; range, 44-83 years)-34 patients deemed unresectable because of arterial involvement and 11 patients deemed unresectable because of extensive venous involvement-were treated with 6 cycles of GTX. Those with arterial involvement were treated with GX/RT after chemotherapy. RESULTS: The GTX and GX/RT treatments were tolerated with the expected drug-related toxicities. There were no bowel perforations, cases of pancreatitis, or delayed strictures. Among those with arterial involvement, 29 underwent subsequent resection, with 20 (69%) achieving R0 resections. All 11 patients with venous-only involvement underwent resection, with 8 achieving R0 resections and 3 achieving complete pathologic responses. For the arterial arm, the 1-year survival rate was 71% (24 of 34 patients), and the median survival was 29 months (95% confidence interval, 21-38 months). Thirteen patients (38%) have not relapsed (range, 5-49+ months). For the venous arm, the median survival has not been reached at more than 42 months. Six patients (55%) in the venous arm did not experience recurrence (range, 6.2-42+ months). CONCLUSIONS: GTX plus GX/RT is an effective neoadjuvant regimen that can be safely administered to patients up to at least the age of 83 years. It is associated with a high response rate, a high rate of R0 resections, and prolonged overall survival.

Establishing a quantitative benchmark for morbidity in pancreatoduodenectomy using ACS-NSQIP, the Accordion Severity Grading System, and the Postoperative Morbidity Index.

OBJECTIVE: The study aim was to quantify the burden of complications of pancreatoduodenectomy (PD). BACKGROUND: The Postoperative Morbidity Index (PMI) is a quantitative measure of the average burden of complications of a procedure. It is based on highly validated systems--ACS-NSQIP and the Modified Accordion Severity Grading System. METHODS: Nine centers contributed ACS-NSQIP complication data for 1589 patients undergoing PD from 2005 to 2011. Each complication was assigned a severity weight ranging from 0.11 for the least severe complication to 1.00 for postoperative death, and PMI was derived. Contribution to total burden by each complication grade was used to generate a severity profile ("spectrogram") for PD. Associations with PMI were determined by regression analysis. RESULTS: ACS-NSQIP complications occurred in 528 cases (33.2%). The non-risk-adjusted PMI was 0.115 (SD = 0.023) for all centers and 0.113 (SD = 0.005) for the 7 centers that contributed at least 100 cases. Grade 2 complications were predominant in frequency, and the most common complication was postoperative bleeding/transfusion. Frequency and burden of complications differed markedly. For instance, severe complications (grades 4/5/6) accounted for only about 20% of complications but for more than 40% of the burden of complications. Organ space infection had the highest burden of any complication. The average burden in cases in which a complication actually occurred was 0.346. CONCLUSIONS: This study develops a quantitative non-risk-adjusted benchmark for postoperative morbidity of PD. The method quantifies the burden of types and grades of postoperative complications and should prove useful in identifying areas that require quality improvement.

The role of molecular analysis in the diagnosis and surveillance of pancreatic cystic neoplasms.

CONTEXT: Molecular analysis of pancreatic cyst fluid obtained by EUS-FNA may increase diagnostic accuracy. We evaluated the utility of cyst-fluid molecular analysis, including mutational analysis of K-ras, loss of heterozygosity (LOH) at tumor suppressor loci, and DNA content in the diagnoses and surveillance of pancreatic cysts. METHODS: We retrospectively reviewed the Columbia University Pancreas Center database for all patients who underwent EUS/FNA for the evaluation of pancreatic cystic lesions followed by surgical resection or surveillance between 2006-2011. We compared accuracy of molecular analysis for mucinous etiology and malignant behavior to cyst-fluid CEA and cytology and surgical pathology in resected tumors. We recorded changes in molecular features over serial encounters in tumors under surveillance. Differences across groups were compared using Student's t or the Mann-Whitney U test for continuous variables and the Fisher's exact test for binary variables. RESULTS: Among 40 resected cysts with intermediate-risk features, molecular characteristics increased the diagnostic yield of EUS-FNA (n=11) but identified mucinous cysts less accurately than cyst fluid CEA (P=0.21 vs. 0.03). The combination of a K-ras mutation and ≥2 loss of heterozygosity was highly specific (96%) but insensitive for malignant behavior (50%). Initial data on surveillance (n=16) suggests that molecular changes occur frequently, and do not correlate with changes in cyst size, morphology, or CEA. CONCLUSIONS: In intermediate-risk pancreatic cysts, the presence of a K-ras mutation or loss of heterozygosity suggests mucinous etiology. K-ras mutation plus ≥2 loss of heterozygosity is strongly associated with malignancy, but sensitivity is low; while the presence of these mutations may be helpful, negative findings are uninformative. Molecular changes are observed in the course of cyst surveillance, which may be significant in long-term follow-up.

Quality of life in patients after total pancreatectomy is comparable with quality of life in patients who undergo a partial pancreatic resection.

BACKGROUND: Quality of life after total pancreatectomy (TP) is perceived to be poor secondary to insulin-dependent diabetes and pancreatic insufficiency. As a result, surgeons may be reluctant to offer TP for benign and premalignant pancreatic diseases. METHODS: We retrospectively reviewed presenting features, operative characteristics, and postoperative outcomes of all patients who underwent TP at our institution. Quality of life was assessed using institutional questionnaires and validated general, pancreatic disease-related, and diabetes-related instruments (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ-C30 and module EORTC-PAN26], Audit of Diabetes Dependent Quality of Life), and compared with frequency-matched controls, patients after a pancreaticoduodenectomy (PD). Continuous variables were compared using Student t-test or analysis of variance. Categorical variables were compared using χ(2) or Fisher exact test. RESULTS: Between 1994 and 2011, 77 TPs were performed. Overall morbidity was 49%, but only 15.8% patients experienced a major complication. Perioperative mortality was 2.6%. Comparing 17 TP and 14 PD patients who returned surveys, there were no statistically significant differences in quality of life in global health, functional status, or symptom domains of EORTC QLQ-C30 or in pancreatic disease-specific EORTC-PAN26. TP patients had slightly but not significantly higher incidence of hypoglycemic events as compared with PD patients with postoperative diabetes. A negative impact of diabetes assessed by Audit of Diabetes Dependent Quality of Life did not differ between TP and PD. Life domains most negatively impacted by diabetes involved travel and physical activity, whereas self-confidence, friendships and personal relationships, motivation, and feelings about the future remained unaffected. CONCLUSIONS: Although TP-induced diabetes negatively impacts select activities and functions, overall quality of life is comparable with that of patients who undergo a partial pancreatic resection.

Expanding the indications for laparoscopic retroperitoneal adrenalectomy: experience with 81 resections.

BACKGROUND: Laparoscopic retroperitoneal (RP) adrenalectomy has gained popularity as the preferred approach over transabdominal (TA) method; however, surgeons have been reluctant to offer this operation to obese patients because of the concerns over inadequate working space and overall perceived higher rate of complications. The aim of the present study was to evaluate the feasibility and safety of RP adrenalectomy compared with TA adrenalectomy, specifically in morbidly obese patients. METHODS: All laparoscopic adrenalectomies performed at our institution between 2004 and 2012 were reviewed retrospectively. Presenting features, operative characteristics, and postoperative outcomes were evaluated. Complications were graded using Clavien system. Continuous variables were compared using Student t-test. Categorical variables were compared using χ(2)-test. Prediction models were constructed using linear or logistic regression as appropriate. RESULTS: Eighty-one RP and 130 TA procedures were performed, 26 (12.3%) and 60 (28.4%), respectively in obese patients (BMI > 30). Among the obese patients, operative time and estimated blood loss were less for RP (90 versus 130 min; P < 0.001 and 0 versus 50 mL; P < 0.001). Differences in the length of stay, overall mortality, incidence and severity of postoperative complications, and rates of readmission were not statistically significant between RP and TA procedures for all comers and in the obese patients. Controlling the operative characteristics and patient-specific factors, neither operative approach nor obesity was found to independently predict the postoperative complications. CONCLUSIONS: Laparoscopic RP adrenalectomy is a safe and feasible technique for obese patients. In the obese patients and for all comers, it offers shorter operative time, decreased estimated blood loss, with comparable length of stay and morbidity and mortality rates. We therefore recommend that this technique should be considered for patients undergoing adrenal resection.

Limitations of ACS-NSQIP in reporting complications for patients undergoing pancreatectomy: underscoring the need for a pancreas-specific module.

BACKGROUND: Large centralized databases are used with increasing frequency for reporting hospital-specific and nationwide trends and outcomes after various surgical procedures in order to improve quality of surgical care. American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) is a risk-adjusted, case-weighted complication tracking initiative that reports 30-day outcomes from more than 400 academic and community institutions in the US. However, the accuracy of event reporting specific to pancreatic surgery has never been examined in depth. METHODS: We retrospectively reviewed medical records of patients, the information on whose postoperative course was originally reported through ACS-NSQIP between 2006 and 2010. Preoperative characteristics, operative data, and postoperative events were recorded after review of electronic medical records including physician and nursing notes, operative room records and anesthesiologist reports. Fidelity of reported clinical events was assessed. Accuracy, sensitivity, and specificity were calculated for each variable of interest. RESULTS: Two hundred and forty-nine pancreatectomies were reviewed, including 145 (58.2 %) Whipple procedures, 19 (7.6 %) total pancreatectomies, 65 (26.1 %) distal pancreatectomies, and 15 (6.0 %) central or partial resections. Median age was 65.7, males comprised 41.5 % of the group, and 74.3 % of patients were Caucasian. The overall rate of complications reported by NSQIP was 44.0 %, compared with 45.0 % in our review, however discordance was observed in 27.3 % of the time, including 34 cases of reporting a complication where there was not one, and 34 cases of missed complication. The most frequently reported event was postoperative bleeding requiring transfusion, however this was also the event most commonly misclassified. Additionally, three procedures unrelated to the index operation were recorded as reoperation events. While a pancreas-specific module does not yet exist, ACS-NSQIP reports a 7.6 % rate of organ-space surgical site infections; when compared with our institutional rate of Grades B and C postoperative fistula (10.4 %), we observed discordance 4.4 % of the time. Delayed gastric emptying, a common post-pancreatectomy morbidity, was not captured at all. Additionally, there were significant inaccuracies in reporting urinary tract infections, postoperative pneumonia, wound complications, and postoperative sepsis, with discordance rates of 4.4, 3.2, 3.6, and 6.8 %, respectively. CONCLUSIONS: ACS-NSQIP data are an important and valuable tool for evaluating quality of surgical care, however pancreatectomy-specific postoperative events are often misclassified, underscoring the need for a hepatopancreatobiliary-specific module to better capture key outcomes in this complex and unique patient population.

Routine intraoperative hepatic sonography does not affect staging or postsurgical hepatic recurrence in pancreatic adenocarcinoma.

OBJECTIVES: The purpose of this study was to evaluate the utility of intraoperative sonography of the liver in the staging of pancreatic adenocarcinoma and its impact on the rate of postoperative tumor recurrence in the liver. METHODS: We performed a retrospective analysis of the rate in which intraoperative sonography of the liver changed surgical management in 470 surgical candidates with pancreatic adenocarcinoma. In postsurgical patients, we performed a χ(2) analysis to examine whether the patients who underwent hepatic intraoperative sonography had a lower rate of recurrent disease in the liver within the first 6 months of surgery compared to patients who did not undergo the procedure. RESULTS: Hepatic intraoperative sonography affected management in less than 1% of cases, detecting 1 unsuspected liver metastasis in 470 surgical patients with pancreatic adenocarcinoma. Of 3 patients with equivocal liver lesions identified on preoperative computed tomography or magnetic resonance imaging, hepatic intraoperative sonography excluded metastasis and cleared all the patients for surgical resection. There was no significant difference in postoperative liver recurrence between the group of patients who received intraoperative sonography before resection and patients who did not have the procedure done (P > .99). CONCLUSIONS: Routine intraoperative sonography of the liver does not affect staging of pancreatic adenocarcinoma. It may be useful for evaluating equivocal lesions.

Defining the post-operative morbidity index for distal pancreatectomy.

BACKGROUND: Accurate assessment of complications is critical in analysing surgical outcomes. The post-operative morbidity index (PMI), derived from the Modified Accordion Severity Grading System and American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP), is a quantitative measure of post-operative morbidity. This study utilizes PMI to establish the complication burden for a distal pancreatectomy (DP). METHODS: From 2005-2011, nine centres contributed ACS-NSQIP complication data for 655 DPs. Each complication was assigned an Accordion severity weight ranging from 0.11 for grade 1 to 1.00 for grade 6 (death). The PMI is the sum of complication severity weights divided by the total number of patients. RESULTS: ACS-NSQIP complications occurred in 177 patients (27.0%). The non risk-adjusted PMI for DP is 0.087. Bleeding/Transfusion and Organ Space Infection were the most common complications. Frequency and burden differed across Accordion grades. While grade 4-6 complications represented only 15.4% of complication occurrences, they accounted for 30.4% of the burden. Subgroup analysis demonstrates that the PMI did not vary based on laparoscopic versus open approach or the performance of a splenectomy. DISCUSSION: This study uses two validated systems to quantitatively establish the morbidity of a DP. The PMI allows estimation of both the frequency and severity of complications and thus provides a more comprehensive assessment of risk.

Incidental 68Ga-DOTATATE uptake in thyroid nodules: Is guideline-directed management still appropriate?

BACKGROUND: Fluorodeoxyglucose uptake on positron emission tomography imaging has been shown to be an independent risk factor for malignancy in thyroid nodules. More recently, a new positron emission tomography radiotracer-Gallium-68 DOTATATE-has gained popularity as a sensitive method to detect neuroendocrine tumors. With greater availability of this imaging, incidental Gallium-68 DOTATATE uptake in the thyroid gland has increased. It is unclear whether current guideline-directed management of thyroid nodules remains appropriate in those that are Gallium-68 DOTATATE avid. METHODS: We retrospectively reviewed Gallium-68 DOTATATE positron emission tomography scans performed at our institution from 2012 to 2022. Patients with incidental focal Gallium-68 DOTATATE uptake in the thyroid gland were included. Fine needle aspiration biopsies were characterized via the Bethesda System for Reporting Thyroid Cytopathology. Bethesda III/IV nodules underwent molecular testing (ThyroSeq v3), and malignancy risk ≥50% was considered positive. RESULTS: In total, 1,176 Gallium-68 DOTATATE PET scans were reviewed across 837 unique patients. Fifty-three (6.3%) patients demonstrated focal Gallium-68 DOTATATE thyroid uptake. Nine patients were imaged for known medullary thyroid cancer. Forty-four patients had incidental radiotracer uptake in the thyroid and were included in our study. Patients included in the study were predominantly female sex (75%), with an average age of 62.9 ± 13.9 years and a maximum standardized uptake value in the thyroid of 7.3 ± 5.3. Frequent indications for imaging included neuroendocrine tumors of the small bowel (n = 17), lung (n = 8), and pancreas (n = 7). Thirty-three patients underwent subsequent thyroid ultrasound. Sonographic findings warranted biopsy in 24 patients, of which 3 were lost to follow-up. Cytopathology and molecular testing results are as follows: 12 Bethesda II (57.1%), 6 Bethesda III/ThyroSeq-negative (28.6%), 1 Bethesda III/ThyroSeq-positive (4.8%), 2 Bethesda V/VI (9.5%). Four nodules were resected, revealing 2 papillary thyroid cancers, 1 neoplasm with papillary-like nuclear features, and 1 follicular adenoma. There was no difference in maximum standardized uptake value between benign and malignant nodules (7.0 ± 4.6 vs 13.1 ± 5.7, P = .106). Overall, the malignancy rate among patients with sonography and appropriate follow-up was 6.7% (2/30). Among patients with cyto- or histopathology, the malignancy rate was 9.5% (2/21). There were no incidental cases of medullary thyroid cancer. CONCLUSION: The malignancy rate among thyroid nodules with incidental Gallium-68 DOTATATE uptake is comparable to rates reported among thyroid nodules in the general population. Guideline-directed management of thyroid nodules remains appropriate in those with incidental Gallium-68 DOTATATE uptake.

Enhanced Complement Expression in the Tumor Microenvironment Following Neoadjuvant Therapy: Implications for Immunomodulation and Survival in Pancreatic Ductal Adenocarcinoma.

Background: Neoadjuvant therapy (NAT) is increasingly being used for pancreatic ductal adenocarcinoma (PDAC) treatment. However, its specific effects on carcinoma cells and the tumor microenvironment (TME) are not fully understood. This study aims to investigate how NAT differentially impacts PDAC's carcinoma cells and TME. Methods: Spatial transcriptomics was used to compare gene expression profiles in carcinoma cells and the TME between 23 NAT-treated and 13 NAT-naïve PDAC patients, correlating with their clinicopathologic features. Analysis of an online single-nucleus RNA sequencing (snRNA-seq) dataset was performed for validation of the specific cell types responsible for NAT-induced gene expression alterations. Results: NAT not only induces apoptosis and inhibits proliferation in carcinoma cells but also significantly remodels the TME. Notably, NAT induces a coordinated upregulation of multiple key complement genes (C3, C1S, C1R, C4B and C7) in the TME, making the complement pathway one of the most significantly affected pathways by NAT. Patients with higher TME complement expression following NAT exhibit improved overall survival. These patients also exhibit increased immunomodulatory and neurotrophic cancer-associated fibroblasts (CAFs); more CD4+ T cells, monocytes, and mast cells; and reduced immune exhaustion gene expression. snRNA-seq analysis demonstrates C3 complement was specifically upregulated in CAFs but not in other stroma cell types. Conclusions: NAT can enhance complement production and signaling within the TME, which is associated with reduced immunosuppression in PDAC. These findings suggest that local complement dynamics could serve as a novel biomarker for prognosis, evaluating treatment response and resistance, and guiding therapeutic strategies in NAT-treated PDAC patients.

Body surface area predicts plasma oxaliplatin and pharmacokinetic advantage in hyperthermic intraoperative intraperitoneal chemotherapy.

BACKGROUND: Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) is used to treat peritoneal surface-spreading malignancies to maximize local drug concentrations while minimizing systemic effects. The pharmacokinetic advantage of HIPEC is defined as the intraperitoneal to intravascular ratio of drug concentrations. We hypothesized that body surface area (BSA) would correlate with the pharmacokinetic advantage of HIPEC. Because oxaliplatin is administered in 5 % dextrose, we hypothesized that BSA would correlate with glycemia. METHODS: We collected blood and peritoneal perfusate samples from ten patients undergoing HIPEC with a BSA-based dose of 250 mg/m(2) oxaliplatin, and measured drug concentrations by inductively coupled plasma mass spectrophotometry. We monitored blood glucose for 24 h postoperatively. Areas under concentration-time curves (AUC) were calculated by trapezoidal rule. Pharmacokinetic advantage was calculated by (AUC[peritoneal fluid]/AUC[plasma]). We used linear regression to test for statistical significance. RESULTS: Higher BSA was associated with lower plasma oxaliplatin AUC (p = 0.0075) and with a greater pharmacokinetic advantage (p = 0.0198) over the 60-minute duration of HIPEC. No statistically significant relationships were found between BSA and blood glucose AUC or peak blood glucose levels. CONCLUSIONS: Higher BSA is correlated with lower plasma drug levels and greater pharmacokinetic advantage in HIPEC, likely because of increased circulating blood volume with inadequate time for equilibration. Plasma glucose levels after oxaliplatin HIPEC were not clearly related to BSA.

Readmission after pancreatic resection is not an appropriate measure of quality.

BACKGROUND: Hospital readmission has been proposed as a metric for quality of medical and surgical care. We examined our institutional experience with readmission after pancreatic resection, and assessed factors predictive of readmission. METHODS: We reviewed 787 pancreatic resections performed at a single institution between 2006 and 2010. Univariate and multivariate logistic regression models were used to assess the relationships between preoperative and postoperative characteristics and readmission. Reasons for hospital readmission were examined in detail. RESULTS: We found the 30-day readmission rate after pancreatic resection to be 11.6 %. In univariate analysis, young age, pancreaticoduodenectomy versus other operations, open versus laparoscopic technique, fistula formation, the need for reoperation, and any complication during the index hospitalization were predictive of readmission. In multivariate analysis, only young age and postoperative complication were predictive of readmission. Vascular resection, postoperative ICU care, length of stay, and discharge disposition were not associated with readmission. The most common reasons for readmission were leaks, fistulas, abscesses, and wound infections (45.1 %), delayed gastric emptying (12.1 %), venous thrombosis (7.7 %), and GI bleeding (7.7 %). CONCLUSIONS: We found the vast majority of readmissions after pancreatic resection were to manage complications related to the operation and were not due to poor coordination of care or poor discharge planning. Because evidence-based measures to prevent these surgical complications do not exist, we cannot support the use of readmission rates themselves as a quality indicator after pancreatic surgery.

Quantitative X-ray computed tomography peritoneography in malignant peritoneal mesothelioma patients receiving intraperitoneal chemotherapy.

BACKGROUND: Intraperitoneal chemotherapy is used to treat peritoneal surface-spreading malignancies. We sought to determine whether volume and surface area of the intraperitoneal chemotherapy compartments are associated with overall survival and posttreatment glomerular filtration rate (GFR) in malignant peritoneal mesothelioma (MPM) patients. METHODS: Thirty-eight MPM patients underwent X-ray computed tomography peritoneograms during outpatient intraperitoneal chemotherapy. We calculated volume and surface area of contrast-filled compartments by semiautomated computer algorithm. We tested whether these were associated with overall survival and posttreatment GFR. RESULTS: Decreased likelihood of mortality was associated with larger surface areas (p = 0.0201) and smaller contrast-filled compartment volumes (p = 0.0341), controlling for age, sex, histologic subtype, and presence of residual disease >0.5 cm postoperatively. Larger volumes were associated with higher posttreatment GFR, controlling for pretreatment GFR, body surface area, surface area, and the interaction between body surface area and volume (p = 0.0167). DISCUSSION: Computed tomography peritoneography is an appropriate modality to assess for maldistribution of intraperitoneal chemotherapy. In addition to identifying catheter failure and frank loculation, quantitative analysis of the contrast-filled compartment's surface area and volume may predict overall survival and cisplatin-induced nephrotoxicity. Prospective studies should be undertaken to confirm and extend these findings to other diseases, including advanced ovarian carcinoma.

Bowel obstruction in elderly ovarian cancer patients: a population-based study.

PURPOSE: Bowel obstruction is a common pre-terminal event in abdominal/pelvic cancer that has mainly been described in small single-institution studies. We used a large, population-based database to investigate the incidence, management, and outcomes of obstruction in ovarian cancer patients. PATIENTS AND METHODS: We identified patients with stages IC-IV ovarian cancer, aged 65 years or older, in the Surveillance, Epidemiology and End Results (SEER)-Medicare database diagnosed between January 1, 1991 and December 31, 2005. We modeled predictors of inpatient hospitalization for bowel obstruction after cancer diagnosis, categorized management of obstruction, and analyzed the associations between treatment for obstruction and outcomes. RESULTS: Of 8607 women with ovarian cancer, 1518 (17.6%) were hospitalized for obstruction subsequent to cancer diagnosis. Obstruction at cancer diagnosis (HR=2.17, 95%CI: 1.86-2.52) and mucinous tumor histology (HR=1.45, 95%CI: 1.15-1.83) were associated with increased risk of subsequent obstruction. Surgical management of obstruction was associated with lower 30-day mortality (13.4% in women managed surgically vs. 20.2% in women managed non-surgically), but equivalent survival after 30 days and equivalent rates of post-obstruction chemotherapy. Median post-obstruction survival was 382 days in women with obstructions of adhesive origin and 93 days in others. CONCLUSION: In this large-scale, population-based assessment of patients with advanced ovarian cancer, nearly 20% of women developed bowel obstruction after cancer diagnosis. While obstruction due to adhesions did not signal the end of life, all other obstructions were pre-terminal events for the majority of patients regardless of treatment.

Management and outcomes of bowel obstruction in patients with stage IV colon cancer: a population-based cohort study.

BACKGROUND: Bowel obstruction is a common complication of late-stage abdominal cancer, especially colon cancer, which has been investigated predominantly in small, single-institution studies. OBJECTIVE: We used a large, population-based data set to explore the surgical treatment of bowel obstruction and its outcomes after hospitalization for obstruction among patients with stage IV colon cancer. DESIGN: This was a retrospective cohort study. SETTING AND PATIENTS: We identified 1004 patients aged 65 years or older in the Surveillance, Epidemiology and End Results-Medicare database diagnosed with stage IV colon cancer January 1, 1991 to December 31, 2005, who were later hospitalized for bowel obstruction. MAIN OUTCOME MEASURES: We describe outcomes after hospitalization and analyzed the associations between surgical treatment of obstruction and outcomes. RESULTS: Hospitalization for bowel obstruction occurred a median of 7.4 months after colon cancer diagnosis, and median survival after obstruction was approximately 2.5 months. Median hospitalization for obstruction was about 1 week and in-hospital mortality was 12.7%. Between discharge and death, 25% of patients were readmitted to the hospital at least once for obstruction, and, on average, patients lived 5 days out of the hospital for every day in the hospital between obstruction diagnosis and death. Survival was 3 times longer in those whose obstruction claims suggested an adhesive obstruction origin. In multivariable models, surgical compared with nonsurgical management was not associated with prolonged survival (p = 0.134). LIMITATIONS: Use of an administrative database did not allow determination of quality of life or relief of obstruction as an outcome, nor could nonsurgical interventions, eg, endoscopic stenting or octreotide, be assessed. CONCLUSIONS: In this population-based study of patients with stage IV colon cancer who had bowel obstruction, overall survival following obstruction was poor irrespective of treatment. Universally poor outcomes suggest that a diagnosis of obstruction in the setting of advanced colon cancer should be considered a preterminal event.

An update on surgical staging of patients with pancreatic cancer.

Accurate staging of pancreatic adenocarcinoma is a crucial step in determining the appropriate therapeutic approach to pancreatic cancer and to maximizing life expectancy. Despite the availability of high-quality abdominal imaging, the use of multi-modality imaging and of diagnostic laparoscopy, a portion of surgically explored patients fail to undergo resection secondary to metastatic disease. This review is an update from the 2012 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium of new developments in the staging of localized pancreatic adenocarcinoma. (Abstracts #168, #177, and #212).

Management of borderline resectable pancreatic adenocarcinoma.

Pancreatic adenocarcinoma is the fourth most common cause of cancer-related death among U.S. men and women. Despite much effort in translational research, pancreatic adenocarcinoma remains a challenging disease with an overall 5-year survival rate less than 5%. To date, the only potentially curative treatment for managing pancreatic adenocarcinoma is surgical resection. However, more than 80% of patients are deemed either unresectable or metastatic upon diagnosis. For borderline resectable disease, although there is no high-level evidence supporting its use, an initial approach involving neoadjuvant therapy is preferred, as opposed to immediate surgery. In this year's ASCO Gastrointestinal Cancers Symposium, several studies were presented with approaches towards treating borderline resectable pancreatic adenocarcinoma. Retrospective studies (Abstract #280, #304, #327) were presented and showed that neoadjuvant chemoradiation were associated with higher rates of negative margin resection and better survival. The tolerability of accelerated fraction radiotherapy with concomitant capecitabine was demonstrated in a phase I study (Abstract #329). More effective therapeutic approaches and prospective studies are needed for this devastating illness. This highlight article will focus on the management of borderline resectable pancreatic adenocarcinoma.