Early Postoperative Extubation is Associated with Shorter Hospitalization and Improved Short-Term Survival in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is associated with significant operative time, hospital resources, and morbidity. We examine factors associated with hospital length of stay (LOS) and early overall survival (OS) after CRS/HIPEC. MATERIALS AND METHODS: Patients who underwent CRS/HIPEC were evaluated for factors associated with LOS. Institutional learning curve influence was addressed by comparing early vs late cohorts. Variables with P < .200 after univariate analysis were considered for inclusion in multivariate linear regression modeling. Independent factors associated with OS were evaluated using the Kaplan-Meier method. RESULTS: Seventy patients underwent CRS/HIPEC (mean age 52.3 years, 64.3% female, and 68.6% Caucasian). Presence of any surgical complication was found in 26 (37.1%), 28 (40%) remained intubated postoperatively, and the mean Peritoneal Carcinomatosis Index (PCI) score was 14.4 (±10.4). Mean intensive care unit and hospital LOS were 2.9 days (±2.3) and 9.6 days (±3.6), respectively. After adjusting for covariates, only shorter time to postoperative ambulation (regression coefficient .92, P = .001) and early extubation (regression coefficient -1.90, P = .018) were associated with decreased hospital LOS on multivariate analysis. Immediate postoperative extubation conferred an independent early survival benefit on Kaplan-Meier analysis (mean OS 714.8 vs 473.4 days, P = .010). There was no difference in hospital LOS or OS between early and late cohorts. CONCLUSION: Early postoperative extubation and shorter time to ambulation are associated with decreased hospital LOS. Moreover, CRS/HIPEC patients extubated immediately postoperatively have an early survival benefit. Every effort should be made to achieve early postoperative extubation and mobilization in CRS/HIPEC patients.

Desmoplastic Small Round Cell Tumor: Long-Term Complications After Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare intra-abdominal soft tissue sarcoma affecting adolescents and young adults. Cytoreduction, hyperthermic intraperitoneal chemotherapy (CRS/HIPEC), and adjuvant radiotherapy may improve local control. We review our experience with patients who undergo CRS/HIPEC and adjuvant radiotherapy for DSRCT. METHODS: A retrospective review was performed for patients with DSRCT from 2013 to 2017 who underwent CRS/HIPEC. Clinicopathologic, operative, and outcome data were reviewed. RESULTS: Ten CRS/HIPEC procedures were performed for nine patients (7 males, 6 Caucasian, median age 19 years (range 10-24)). Four patients presented with extra-abdominal disease; five had liver involvement. The median peritoneal cancer index was 16 (range 5-20). All received neoadjuvant chemotherapy. CCR 0/1 resection was possible in nine patients. Major complications occurred in four with no operative mortalities. All received adjuvant chemotherapy, seven received radiation therapy, and three received stem-cell transplant. All but one patient recurred after treatment. The median recurrence-free and overall survival (OS) were 12 and 45 months (95% confidence interval 35.1-54.9) respectively, with a 3-year OS of 55%. Long-term parenteral nutrition was required in eight for a median of 261 days (range 37-997). Clinically significant long-term complications requiring further surgery included gastroparesis (N = 1), small bowel obstruction (N = 3) and hemorrhagic cystitis (N = 2). CONCLUSIONS: Multimodal therapy for DSRCT consisting of multiagent neoadjuvant chemotherapy, CRS/HIPEC, adjuvant chemotherapy, and radiation therapy is associated with potential cumulative toxicity. Recurrence after resection is common. Prolonged parenteral nutrition may be necessary, and late gastrointestinal and genitourinary complications may require additional treatment.

Role of Adjuvant Multimodality Therapy After Curative-Intent Resection of Ampullary Carcinoma.

Importance: Ampullary adenocarcinoma is a rare malignant neoplasm that arises within the duodenal ampullary complex. The role of adjuvant therapy (AT) in the treatment of ampullary adenocarcinoma has not been clearly defined. Objective: To determine if long-term survival after curative-intent resection of ampullary adenocarcinoma may be improved by selection of patients for AT directed by histologic subtype. Design, Setting, and Participants: This multinational, retrospective cohort study was conducted at 12 institutions from April 1, 2000, to July 31, 2017, among 357 patients with resected, nonmetastatic ampullary adenocarcinoma receiving surgery alone or AT. Cox proportional hazards regression was used to identify covariates associated with overall survival. The surgery alone and AT cohorts were matched 1:1 by propensity scores based on the likelihood of receiving AT or by survival hazard from Cox modeling. Overall survival was compared with Kaplan-Meier estimates. Exposures: Adjuvant chemotherapy (fluorouracil- or gemcitabine-based) with or without radiotherapy. Main Outcomes and Measures: Overall survival. Results: A total of 357 patients (156 women and 201 men; median age, 65.8 years [interquartile range, 58-74 years]) underwent curative-intent resection of ampullary adenocarcinoma. Patients with intestinal subtype had a longer median overall survival compared with those with pancreatobiliary subtype (77 vs 54 months; P = .05). Histologic subtype was not associated with AT administration (intestinal, 52.9% [101 of 191]; and pancreatobiliary, 59.5% [78 of 131]; P = .24). Patients with pancreatobiliary histologic subtype most commonly received gemcitabine-based regimens (71.0% [22 of 31]) or combinations of gemcitabine and fluorouracil (12.9% [4 of 31]), whereas treatment of those with intestinal histologic subtype was more varied (fluorouracil, 50.0% [17 of 34]; gemcitabine, 44.1% [15 of 34]; P = .01). In the propensity score-matched cohort, AT was not associated with a survival benefit for either histologic subtype (intestinal: hazard ratio, 1.21; 95% CI, 0.67-2.16; P = .53; pancreatobiliary: hazard ratio, 1.35; 95% CI, 0.66-2.76; P = .41). Conclusions and Relevance: Adjuvant therapy was more frequently used in patients with poor prognostic factors but was not associated with demonstrable improvements in survival, regardless of tumor histologic subtype. The value of a multimodality regimen remains poorly defined.

Anesthesia and Pain Management for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Desmoplastic Small Round Cell Tumors in Children, Adolescents, and Young Adults.

BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive sarcoma. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may improve survival. METHODS: A retrospective review of anesthetic management and postoperative pain control strategies after CRS/HIPEC for DSRCT from 2013 to 2017 was performed. RESULTS: The review analyzed 10 CRS/HIPEC procedures performed for nine DSRCT patients with a median age of 19 years (range 10-24 years). Six of these patients were Caucasian, and seven were men. The median operative duration was 551 min (range 510-725 min), and the median anesthesia duration was 621 min (range 480-820 min). Postoperative mechanical ventilation was necessary in 5 patients for a median duration of 1 day (range 0-2 days). The median intraoperative intravenous fluid administration was 13 ml/kg/h (range 6.3-24.4 ml/kg/h), and the colloid administration was 12 ml/kg (range 0.0-53.0 ml/kg). The median blood loss was 15 ml/kg (range 6.3-77.2 ml/kg). Nine patients received intraoperative transfusion with a median red blood cell transfusion volume of 14 ml/kg (range 10.1-58.5 ml/kg). The median intraoperative urine output was 2 ml/kg/h (range 0.09-8.40 ml/kg/h), and half of the patients received intraoperative diuretics. Cisplatin was used during HIPEC for eight surgeries. Acute kidney injury was observed in two patients, one of whom required short-term dialysis. Epidural infusions were used in eight cases for a median of 4 days (range 3-5 days). Postoperative intravenous opioid use (morphine equivalent) was 0.67 mg/kg/day (range 0.1-9.2 mg/kg/day) administered for a median of 11 days (range 2-35 days). CONCLUSION: Cytoreduction and HIPEC for DSRCT are associated with significant perioperative fluid requirements and potentially challenging pain management. Renal protective strategies should be considered for reduction of cisplatin-associated nephrotoxicity. Further investigation for a more effective, less systemically toxic HIPEC agent is warranted.

The Impact of Ostomy Creation after Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy in a Newly Established Peritoneal Malignancy Program.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has improved outcomes for selected patients with peritoneal carcinomatosis and often requires ostomy creation. We examined the impact of ostomy creation in a newly established peritoneal malignancy program. A retrospective review was performed of CRS-HIPEC procedures from 2011 to 2016. Those who did and did not receive an ostomy were compared. Fifty-eight patients underwent CRS-HIPEC and an ostomy was created in 25.9 per cent. Median peritoneal cancer index (14 vs 16, P = 0.63) and multivisceral resection rates (87.9 vs 100.0%, P = 0.17) were similar between groups. Multivariable analysis revealed that bowel resection (OR 210.65, P = 0.02) was significantly associated with ostomy creation. Advanced age was noted to be inversely associated with stoma formation (OR 0.04, P = 0.04). Progression-free survival was significantly lower in the ostomy group (18 vs 23 months, P = 0.03). Those with an ostomy experienced prolonged length of stay (13.3 ± 7.4 vs 9.5 ± 3.7, P = 0.01). At follow-up, 6/10 temporary ostomies had undergone reversal and three patients experienced morbidity after reversal. Ostomy creation may occur during CRS-HIPEC and carries potential for morbidity. Ostomy creation may contribute to postoperative length of stay. Patients should be counseled preoperatively on the potential impact of ostomy placement during CRS-HIPEC.

The Impact of Early Recurrence on Quality of Life after Cytoreduction with HIPEC.

Improved oncological outcomes after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in highly selected patients have been well documented. The extensive nature of the procedure adversely affects quality of life (QoL). The aim of this study is to longitudinally evaluate QoL following CRS/HIPEC. This is a retrospective review of a prospectively maintained database of patients with peritoneal malignancies undergoing CRS/HIPEC. Clinicopathological data, oncologic outcomes, and QoL were analyzed preoperatively and postoperatively at 2 weeks, and 1, 3, 6, and 12 months. The Functional Assessment of Cancer Therapy-Colorectal instrument was used to determine changes in QoL after CRS/HIPEC and the impact of early recurrence (<12 months) on QoL. Thirty-six patients underwent CRS/HIPEC over 36 months. The median peritoneal cancer index score was 18 and the completeness of cytoreduction-0/1 rate was 97.2 per cent. Postoperative major morbidity was 16.7 per cent with one perioperative death. Disease-free survival was 12.6 months in patients with high-grade tumors versus 31.0 months in those with low-grade tumors (P = 0.03). QoL decreased postoperatively and improved to baseline in six months. Patients with early recurrence had a decrease in global QoL compared with preoperative QoL at 6 (P < 0.03) and 12 months (P < 0.05). This correlation was not found in patients who had not recurred. Patients who undergo CRS/HIPEC have a decrease in QoL that plateaus in 3 to 6 months. Early recurrence adversely impacts QoL at 6 and 12 months. This study emphasizes the importance of patient selection for CRS/HIPEC. The expected QoL trajectory in patients at risk for early recurrence must be carefully weighed against the potential oncological benefit of CRS/HIPEC.

Cytoreduction with hyperthermic intraperitoneal chemotherapy: an appraisal of outcomes and cost at a newly established peritoneal malignancy program.

BACKGROUND: Outcome measures after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for peritoneal carcinomatosis in established centers are well defined. However, results from newly emerging US centers have not been reported. METHODS: This is a retrospective review of a prospectively maintained database of patients with peritoneal malignancies undergoing CRS/HIPEC. RESULTS: Fifty-six patients underwent exploratory laparotomy with 36 receiving CRS/HIPEC over 36 months. The median peritoneal cancer index score was 18, and the cytoreduction 0/1 rate was 92%. Postoperative major morbidity was 16.7% with one perioperative death. The median length of hospital stay and intensive care unit days were 9 and 3 days, respectively. Disease-free survival in high-grade vs low-grade tumors was 12.6 and 31.0 months (P, .03), respectively. Average direct cost for patients undergoing CRS/HIPEC was $25,917. CONCLUSIONS: Our emerging center's short-term results are comparable with established programs with a trend toward more selective intraoperative judgment on who undergoes CRS/HIPEC.

Thyroid carcinoma, version 2.2014.

These NCCN Guidelines Insights focus on some of the major updates to the 2014 NCCN Guidelines for Thyroid Carcinoma. Kinase inhibitor therapy may be used to treat thyroid carcinoma that is symptomatic and/or progressive and not amenable to treatment with radioactive iodine. Sorafenib may be considered for select patients with metastatic differentiated thyroid carcinoma, whereas vandetanib or cabozantinib may be recommended for select patients with metastatic medullary thyroid carcinoma. Other kinase inhibitors may be considered for select patients with either type of thyroid carcinoma. A new section on "Principles of Kinase Inhibitor Therapy in Advanced Thyroid Cancer" was added to the NCCN Guidelines to assist with using these novel targeted agents.

Management of a ruptured mucinous mesenteric cyst with hyperthermic intraperitoneal chemotherapy.

Mesenteric cysts are rare intra-abdominal cysts that are generally regarded as benign, and the incidence of malignancy is often cited to be 3%. The typical recommendation for treatment is complete excision to minimize recurrence. Excision can be performed laparoscopically, but this can lead to intra-abdominal dissemination of the cyst contents. There has been one case report describing the development of pseudomyxoma peritonei following rupture of a mesenteric cyst. We describe the treatment and outcome of a patient who underwent cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for the treatment of an incompletely resected mucinous cystadenocarcinoma originating from the colonic mesentery.

The microbiology of secondary and postoperative pancreatic infections: implications for antimicrobial management.

HYPOTHESIS: We reviewed our experience with secondary pancreatic infections with a focus on preemptive intervention and the potential alteration of the recovered microbial flora. The pathogens associated with postoperative pancreatic infections were analyzed with respect to nonenteric organisms, if any, that were recovered. We hypothesized that our findings might alter the antimicrobial management of these patients. DESIGN: Retrospective review. SETTING: Hospitals affiliated with the University of Tennessee Health Science Center, Memphis. PATIENTS: Patients developing secondary and postoperative pancreatic infections following severe acute pancreatitis. METHODS: Factors examined relative to secondary pancreatitis included preoperative antibiotic use and antecedent extrapancreatic infections potentially implicated in seeding the pancreatic bed. Patients who had elective resection received 24 to 48 hours of antibiotic prophylaxis. RESULTS: Twenty-two patients required surgery for secondary infections following severe acute pancreatitis, with 29 pathogenic isolates being recovered. Of these 22 patients, 14 received vancomycin hydrochloride prior to surgical intervention. Of those 14 patients, 6 had isolates recovered at the time of surgery that were positive for Enterococcus faecalis and 5 of these isolates were vancomycin resistant. Eight of the 22 patients received antifungal prophylaxis with no fungi recovered from intraoperative culture. However, 2 of the 14 patients who did not receive empiric therapy had isolates that were positive for fungi. Five patients who required an urgent operation for sepsis had pathogenic isolates that were similar to those recovered from central lines. Postoperative infections occurred in 40 of 225 patients (17.8%) who had an elective pancreatic resection, with 72 pathogenic isolates being recovered. Of these 40 patients, 22 (55.0%) had polymicrobial infections. Of the 72 pathogenic isolates recovered from patients, 34 (47.2%) were gram-positive organisms, 15 (20.8%) were fungal organisms, and 17 (23.6%) were drug-resistant bacteria. CONCLUSIONS: Prolonged vancomycin use in patients with severe acute pancreatitis is associated with the acquisition of vancomycin-resistant enterococci. Empiric antifungal therapy may reduce the incidence of secondary fungal pancreatic infections. Systemic bloodstream infections at extrapancreatic sites can lead to seeding of pancreatic pseudocysts. Postoperative infections frequently include gram-positive, fungal, and drug-resistant organisms, and empiric therapy directed at these pathogens should be utilized until definitive culture results are obtained.