The Safety of Iterative Cytoreductive Surgery and HIPEC for Peritoneal Carcinomatosis: A High Volume Center Prospectively Maintained Database Analysis.

INTRODUCTION: Offering iterative cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for recurrence of peritoneal carcinomatosis (PC) poses a surgical dilemma. Safety of this repeated operation in the short and long term has not been largely investigated. METHODS: Patients with PC who underwent 377 CRS/HIPEC procedures between 2007 and 2018 at our institution were included from a prospectively maintained database. Outcomes for patients who had singular CRS/HIPEC were compared with those for patients who had repeated CRS/HIPEC. RESULTS: Overall, there were 325 singular and 52 iterative CRS/HIPEC procedures performed during this time period. Age, sex, and ASA class were comparable between cohorts (p = NS). Optimal cytoreduction, mean operative time, mean length of hospital stay, 90-day major morbidity, and 90-day mortality were also similar. At a median follow-up of 24 months, there was no significant difference in recurrence rate (%, 60 vs 63, p = 0.76), disease-free survival (mean months, 19 vs 15, p = 0.30), and overall survival (mean months, 32 vs 27, p = 0.69). The iterative CRS/HIPEC group had significantly higher rates of major late complications than the singular CRS/HIPEC group (%, 18 vs 40, p < 0.01). CONCLUSION: Repeated CRS/HIPEC for PC has similar perioperative morbidity and mortality, as well as long-term oncological benefits, when compared with singular CRS/HIPEC. However, more than twice as many patients undergoing iterative CRS/HIPEC suffered from major late complications.

A unique presentation of superinfected pseudomyxoma peritonei secondary to a low-grade appendiceal mucinous neoplasm.

BACKGROUND: Pseudomyxoma peritonei (PMP) is an uncommon condition characterized by diffuse mucinous material in the abdomen and pelvis, generally arising from a perforated epithelial neoplasm. Typically, the disease presents as suspected acute appendicitis, ovarian mass, abdominal distension, or ventral hernia. Our case represents a very rare presentation of superinfected PMP. CASE PRESENTATION: A 46-year-old female with a past medical history notable for depression, asthma, and uterine leiomyomas presented to an urgent care with 5 days of progressive abdominal pain, bloating, nausea, and subjective fevers. The patient had a diffusely tender abdomen, without peritonitis, was mildly tachycardic, and had a white blood cell count of 15 K. A CT of the abdomen/pelvis was consistent with PMP with a ruptured appendiceal mucocele versus PMP secondary to an adnexal ovarian neoplastic pathology with an infectious component. The patient initially improved on antibiotics but ultimately required two surgeries, the first of which controlled intraabdominal sepsis while the second permitted definitive management of PMP with cytoreductive surgery (CRS) and HIPEC. CONCLUSION: Superinfected PMP is a rare entity with very few documented cases. A staged approach that incorporates clearing the peritoneal infection, with or without resection of the primary tumor, followed by rehabilitation and definitive surgery appears to be a safe and effective management strategy.

Multiagent neoadjuvant chemotherapy and tumor response are associated with improved survival in pancreatic cancer.

BACKGROUND: Neoadjuvant therapy (NT) for borderline resectable pancreatic cancer (BRPC) has evolved to include multi-agent regimens and chemoradiation. We report our experience and compare outcomes of initially resectable pancreatic cancer (IRPC) vs BRPC receiving NT across two eras of chemotherapy regimens. METHODS: Data were collected retrospectively on pancreaticoduodenectomy patients between January 2008 and October 2015. Outcomes and survival were compared based on patient, laboratory and treatment factors. RESULTS: 195 patients were included and 133 had IRPC and 62 BRPC. IRPC operations were shorter (449 min vs 520 min, p = 0.003), had less blood loss (663 ml vs 954 ml, p = 0.002) and involved fewer vascular resections (29% vs 76%, p = 0.002). The rate of R0 resection was identical (82%, p = 1) and the IRPC group had higher node-positive ratio (19.3% vs 7.2% p < 0.0001). 15 patients received a single agent regimen while 47 received multi-agent regimens with 90% receiving radiation.Survival was similar between BRPC and IRPC (log-rank p = 0.7). Histopathologic response (CAP grade 0 or 1) was not associated with survival (p = 0.13), but completion of ≥4 cycles of multi-agent pre-operative chemotherapy (p = 0.001) and complete response to NT (p = 0.04) were significant predictors of survival. CONCLUSIONS: BRPC patients treated with NT have similar morbidity and survival to their IRPC counterparts. Pathologic response and modern NT are associated with improved survival.

Endoscopic Vacuum Therapy via Pharyngostomy: Novel Access for Management of Upper Gastrointestinal Defects.

BACKGROUND: Perforation and anastomotic leakage of the upper gastrointestinal tract (UGI) has a high mortality and morbidity rate. Recently, UGI leaks have been treated with endoscopic vacuum therapy (EVT). However, this technique traditionally requires multiple EVT changes and a prolonged and uncomfortable nasoenteric intubation. We describe our experience using EVT through a novel pharyngostomy access to manage UGI leaks. METHODS: We describe our development and implementation of EVT via a novel pharyngostomy access to treat a variety of UGI defects. Preoperative, perioperative, and postoperative data were analyzed. RESULTS: Six patients with UGI perforations or anastomotic leaks were treated with an EVT using a pharyngostomy access. The median age was 69 years (IQR 53-71). Four patients leaked after an Ivor Lewis esophagectomy, one after a robotic para-esophageal hernia repair, and another after a Roux en Y esophagojejunostomy. Defects were detected on a median of 11.5 days (IQR 3-21). Median values for the duration of the EVT therapy and the number of EVT changes were 19.5 days (IQR 14-31) and 7 (IQR 6.5-9), respectively. Four of the patients were discharged with an EVT in place and were successfully managed as outpatients. At a median follow-up of 8 months, two patients developed strictures. None of the patients required any surgical re-intervention, they tolerated oral intake, and all leakages were confirmed closed by imaging and endoscopy. DISCUSSION: Endoscopic vacuum therapy can be successfully managed through a pharyngostomy access, as described. This access is easy, comfortable, and reliable and allows for a transition to outpatient management.

An endocannabinoid mechanism for stress-induced analgesia.

Acute stress suppresses pain by activating brain pathways that engage opioid or non-opioid mechanisms. Here we show that an opioid-independent form of this phenomenon, termed stress-induced analgesia, is mediated by the release of endogenous marijuana-like (cannabinoid) compounds in the brain. Blockade of cannabinoid CB(1) receptors in the periaqueductal grey matter of the midbrain prevents non-opioid stress-induced analgesia. In this region, stress elicits the rapid formation of two endogenous cannabinoids, the lipids 2-arachidonoylglycerol (2-AG) and anandamide. A newly developed inhibitor of the 2-AG-deactivating enzyme, monoacylglycerol lipase, selectively increases 2-AG concentrations and, when injected into the periaqueductal grey matter, enhances stress-induced analgesia in a CB1-dependent manner. Inhibitors of the anandamide-deactivating enzyme fatty-acid amide hydrolase, which selectively elevate anandamide concentrations, exert similar effects. Our results indicate that the coordinated release of 2-AG and anandamide in the periaqueductal grey matter might mediate opioid-independent stress-induced analgesia. These studies also identify monoacylglycerol lipase as a previously unrecognized therapeutic target.

15-Year Experience with Multimodality Therapy Including Esophagectomy for Elderly Patients with Locoregional Esophageal Cancer.

BACKGROUND: Optimal curative therapy for locally advanced esophageal and esophagogastric junction (EGJ) cancer might not be offered to elderly patients due to patient and treating physician perception of the high risk of therapy. To understand the risk of multimodality curative therapy, including surgical resection in the elderly population, we studied our experience with curative therapy in this patient population and compared the risks and outcomes with those in a younger population. STUDY DESIGN: Between January 1, 2004 and December 31, 2019, four hundred and five consecutive patients with esophageal or EGJ cancer underwent primary treatment at our institution, including esophagectomy. Data collected included demographic information, tumor stage, preoperative Charlson Comorbidity Index scores, treatment variables, and short- and long-term outcomes. Patients who were 70 years or older were classified as the "older" group and patients younger than 70 years were "younger." RESULTS: One hundred and eighty-eight younger (mean age 59 years) and 94 older (mean age 74 years) patients received neoadjuvant chemoradiotherapy and surgical resection for stage II and higher cancer. Preoperative American Society of Anesthesiologist and Charlson Comorbidity Index scores were significantly worse in the older group. Postoperative atrial fibrillation and urinary retention developed more often in the older group. Despite this, the rate of postoperative Clavien-Dindo complication severity scores of 3 or higher, perioperative mortality rates, and lengths of stay were similar. Long-term age-adjusted survival rate was 44.8% at 5 years for the group 70 years or older and 39% for the group younger than 70 years (NS). CONCLUSIONS: Patients 70 years and older with locally advanced esophageal or EGJ cancer should be evaluated for optimal curative therapy including neoadjuvant chemoradiotherapy and surgical resection. Although preoperative risk scoring and postoperative atrial arrythmias are higher in the older group, short- and long-term outcomes are not inferior in these patients.

Role of the basolateral nucleus of the amygdala in endocannabinoid-mediated stress-induced analgesia.

Recent work in our laboratories has demonstrated that an opioid-independent form of stress-induced analgesia (SIA) is mediated by endogenous ligands for cannabinoid receptors-anandamide and 2-arachidonoylglycerol (2-AG) [A.G. Hohmann, R.L. Suplita, N.M. Bolton, M.H. Neely, D. Fegley, R. Mangieri, J.F. Krey, J.M. Walker, P.V. Holmes, J.D. Crystal, A. Duranti, A. Tontini, M. Mor, G. Tarzia, D. Piomelli, An endocannabinoid mechanism for stress-induced analgesia, Nature 435 (2005) 1108-1112]. The present study was conducted to examine the contribution of cannabinoid CB1 receptors in the basolateral nucleus of the amygdala (BLA) and central nucleus of the amygdala (CeA) to nonopioid SIA. SIA was induced by continuous footshock (3 min 0.9 mA) and quantified behaviorally using the tail-flick test. Microinjection of the CB1 antagonist/inverse agonist rimonabant (SR141716A) into the BLA, a limbic forebrain region with high densities of CB1 receptors, suppressed SIA relative to control conditions. By contrast, the same dose administered into the CeA, where CB1 immunoreactivity is largely absent, or outside the amygdala did not alter SIA. To examine the contribution of endocannabinoids in the BLA to SIA, we used selective pharmacological inhibitors of the anandamide-degrading enzyme fatty-acid amide hydrolase (FAAH) and the 2-arachidonoylglycerol-degrading enzyme monoacylglycerol lipase (MGL). The FAAH inhibitor URB597 and MGL inhibitor URB602, at doses that enhanced SIA following microinjection in the midbrain periaqueductal gray, did not alter SIA relative to control conditions. Our findings suggest that CB1 receptors in the BLA but not the CeA contribute to SIA, but pharmacological inhibition of endocannabinoid degradation at these sites does not affect the expression of stress antinociception.