Determinants of Long-term Survival Decades After Esophagectomy for Esophageal Cancer.

BACKGROUND: Long-term survival in esophagectomy patients with esophageal cancer is low due to tumor-related characteristics, with few reports of modifiable variables influencing outcome. We identified determinants of overall survival, time to recurrence, and disease-free survival in this patient cohort. METHODS: Adult patients who underwent esophagectomy for primary esophageal cancer from January 5, 2000, through December 30, 2010, at our institution were identified. Univariate Cox models and multivariable logistic regression analyses were used to identify associations between modifiable and unmodifiable patient and clinical variables and outcome of survival for the total cohort and a subgroup with locally advanced disease. RESULTS: We identified 870 patients with esophageal cancer who underwent esophagectomy. The median follow-up time was 15 years, and the 15-year overall survival rate was 25.2%, survival free of recurrence was 57.96%, and disease-free survival was 24.21%. Decreased overall survival was associated with the following unmodifiable variables: older age, male sex, active smoking status, history of coronary artery disease, advanced clinical stage, and tumor location. Decreased overall survival was associated with the following modifiable variables: use of neoadjuvant therapy, advanced pathologic stage, resection margin positivity, surgical reintervention, and blood transfusion requirement. The overall survival probability 6 years after esophagectomy was 0.920 (95% CI, 0.895-0.947), and time-to-recurrence probability was 0.988 (95% CI, 0.976-1.000), with a total of 17 recurrences and 201 deaths. CONCLUSIONS: Once patients survive 5 years, recurrence is rare. Long-term survival can be achieved in high-volume centers adhering to National Comprehensive Cancer Network guidelines using multidisciplinary care teams that is double what has been previously reported in the literature from national databases.

The Benefits of Local Anesthesia Used in Mastectomy Without Reconstruction.

BACKGROUND: The opioid epidemic has driven renewed interest in local anesthesia to reduce postoperative opioid use. Our objective was to determine if local anesthesia decreased hospital pain scores, oral morphine equivalents (OME), length of stay (LOS), and nausea/vomiting. METHODS: Single institution retrospective study of females who underwent mastectomy without reconstruction. RESULTS: Overall, 712 patients were included; 63 (8.8%) received bupivacaine (B), 512 (72%) liposomal bupivacaine (LB), and 137 (19%) no local. 95% were discharged on POD1. Liposomal bupivacaine use increased from 2014 to 2019. Additional factors associated with use of local regimen were surgeon and extent of axillary surgery. Fewer patients used postop opioids during their hospital stay if any local was used compared to none (76 vs 88%; 0.003). Compared to none, local had shorter mean PACU LOS (95 vs 87 min; P = .02), lower mean intraoperative-OME (96 vs 106; P < .001), and lower mean postoperative OME/hr (1.4 vs 1.8 P = .001). Multivariable analysis (MVA) showed lower OME/hr with LB compared to B and none (P = .002); this translates to 22 mg and 30 mg of oxycodone in a 24-hr period, respectively. MVA showed lower POD1 pain scores with LB relative to none (P = .049). Local did not impact nausea/emesis. CONCLUSION: Local anesthesia was superior to no local in several measures. However, a consistent benefit of a specific local anesthetic agent was not demonstrated (LB vs B). A prospective study is warranted to determine the optimal local regimen for this cohort and further inform clinical relevance.

Patient-Reported Quality of Life Before and After Chemoradiation for Intact Pancreas Cancer: A Prospective Registry Study.

PURPOSE: Our purpose was to determine the effect of chemoradiotherapy (CRT) on patient-reported quality of life (QOL) for patients with intact pancreas cancer. METHODS AND MATERIALS: We reviewed a prospective QOL registry for patients with intact, clinically localized pancreatic ductal adenocarcinoma treated with CRT between June 2015 and November 2018. QOL was assessed pre-CRT (immediately before CRT, after neoadjuvant chemotherapy) and at the completion of CRT with the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) and its component parts: FACT-General (FACT-G) and hepatobiliary cancer subscore (HCS). A minimally important difference from pre-CRT was defined as ≥ 6, 5, and 8 points for FACT-G, HCS, and FACT-Hep, respectively. RESULTS: Of 157 patients who underwent CRT, 100 completed both pre- and post-CRT surveys and were included in the primary analysis. Median age at diagnosis was 65 years (range, 23-90). National Comprehensive Cancer Network resectability status was resectable (3%), borderline resectable (40%), or locally advanced (57%). Folinic acid, 5-fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) (75%) or gemcitabine and nab-paclitaxel (42%) were given for a median of 6 cycles (range, 0-42) before CRT. Radiation therapy techniques included 3-dimensional conformal (22%), intensity modulated photon (55%), and intensity modulated proton (23%) radiation therapy to a median dose of 50 Gy (range, 36-62.5). Concurrent chemotherapy was most commonly capecitabine (82%). Sixty-three patients (63%) had surgery after CRT. The mean decline in FACT-G, HCS subscale, and FACT-Hep from pre- to post-CRT was 3.5 (standard deviation [SD], 13.7), 1.7 (SD 7.8), and 5.2 (SD 19.4), respectively. Each of these changes were statistically significant, but did not meet the minimally important difference threshold. Pancreatic head tumor location was associated with decline in FACT-Hep. Nausea was the toxicity with the greatest increase from pre- to post-CRT by both physician-assessment and patient-reported QOL. CONCLUSIONS: For patients with intact pancreatic adenocarcinoma, modern CRT is well tolerated with minimal decline in QOL during treatment.

The impact of HIPEC vs. EPIC for the treatment of mucinous appendiceal carcinoma: a study from the US HIPEC collaborative.

INTRODUCTION: Mucinous appendiceal carcinoma is a rare malignancy that commonly spreads to the peritoneum leading to peritoneal metastases. Complete cytoreduction with perioperative intraperitoneal chemotherapy (PIC) is the mainstay of treatment, administered as either hyperthermic intra peritoneal chemotherapy (HIPEC) or early post-operative intraperitoneal chemotherapy (EPIC). Our goal was to assess the perioperative and long term survival outcomes associated with these two PIC methods. MATERIALS AND METHODS: Patients with mucinous appendiceal carcinoma were identified in the US HIPEC Collaborative database from 12 academic institutions. Patient demographics, clinical characteristics, and survival outcomes were compared among patients who underwent HIPEC vs. EPIC with inverse probability weighting (IPW) used for adjustment. RESULTS: Among 921 patients with mucinous appendiceal carcinoma, 9% underwent EPIC while 91% underwent HIPEC. There was no difference in Grade III-V complications between the two groups (18.5% for HIPEC vs. 15.0% for EPIC, p=.43) though patients who underwent HIPEC had higher rates of readmissions (21.2% vs. 8.8%, p<.01). Additionally, PIC method was not an independent predictor for overall survival (OS) or recurrence-free survival (RFS) after adjustment on multivariable analysis. CONCLUSIONS: Among patients with mucinous appendiceal carcinoma, both EPIC and HIPEC appear to be associated with similar perioperative and long-term outcomes.

Effects of psychosensory stimulation on anal pressures: Effects of alfuzosin.

BACKGROUND: Our aim is to explain the lack of clarity in the ways in which anxiety and depression, which are common in defecatory disorders (DD), may contribute to the disorder. In this study, we evaluate the effects of mental stress and relaxation on anal pressures and the mechanisms thereof. METHODS: In 38 healthy women and 36 DD patients, rectoanal pressures were assessed at rest and during mental stressors (ie, word-color conflict [Stroop] and mental arithmetic tests) and mental relaxation, before and after randomization to placebo or the adrenergic α1 -antagonist alfuzosin. KEY RESULTS: During the baseline Stroop test, the anal pressure increased by 6 ± 13 mm Hg (mean ± SD, P = 0.004) in healthy women and 9 ± 10 mm Hg (P = 0.0001) in constipated women. During mental arithmetic, the anal pressure increased in healthy (4 ± 8 mm Hg, P = 0.002) and constipated women (5 ± 9 mm Hg, P = 0.004). After relaxation, anal pressure declined (P = 0.0004) by 3 ± 4 mm Hg in DD patients but not in controls. Alfuzosin reduced (P = 0.0001) anal resting pressure (by 31 ± 19 mm Hg) vs placebo (16 ± 18 mm Hg). However, during the postdrug Stroop test, anal pressure increased (P = 0.0001) in participants who received alfuzosin but not placebo. CONCLUSIONS & INFERENCES: In healthy controls and DD patients, mental stressors likely increased anal pressure by contracting the internal anal sphincter; relaxation reduced anal pressure in DD patients. Alfuzosin reduced anal resting pressure but did not block the Stroop-mediated contractile response, which suggests that this response is not entirely mediated by adrenergic α1 receptors.

Multiphase Computed Tomographic Enterography: Diagnostic Yield and Efficacy in Patients With Suspected Small Bowel Bleeding.

OBJECTIVE: To estimate the diagnostic yield and efficacy of multiphase computed tomographic enterography (mpCTE) for suspected small bowel bleeding in routine clinical practice. PATIENTS AND METHODS: All mpCTEs performed between January 1, 2006, and December 31, 2014, for suspected small bowel bleeding were included and classified by a gastroenterologist and an abdominal radiologist. The reference standard for a definitive diagnosis was balloon-assisted enteroscopic, angiographic, surgical, or pathologic results. Overall and lesion-specific diagnostic yield (DY), sensitivity, and positive predictive value were calculated. The relationship of mpCTE diagnosis and continued bleeding or iron supplementation was examined using logistic regression in patients with at least 1 year of follow-up. RESULTS: We identified 1087 patients who had an initial mpCTE indication of small bowel bleeding. The overall DY was 31.6% (344 of 1087 patients; 95% CI, 29.0%-35.0%), higher for an indication of small bowel bleeding that was overt or occult with heme-positive stool vs occult with only iron-deficiency anemia (DY, 35.0% [170 of 486] and 35.3% [66 of 187] vs 26.1% [108 of 414]; P=.004 and P=.02, respectively). The highest sensitivity and positive predictive value were for small bowel masses (90.2% [55 of 61] and 98.2% [55 of 56], respectively). Higher risk of future bleeding and iron supplementation was seen with a negative result on mpCTE (odds ratio [OR], 1.91; 95% CI, 1.28-2.86), lack of surgical intervention (OR, 4.37; 95% CI, 2.31-8.29), or discrepant balloon-assisted enteroscopic findings (OR, 2.50; 95% CI, 1.03-6.09). CONCLUSION: Multiphase computed tomographic enterography has a higher rate of detection in patients with overt bleeding or heme-positive stool. The procedure provides actionable targets for further intervention and leads to substantially reduced rates of rebleeding in long-term follow-up.

Identification of Site-specific Recurrence Following Primary Radiation Therapy for Prostate Cancer Using C-11 Choline Positron Emission Tomography/Computed Tomography: A Nomogram for Predicting Extrapelvic Disease.

BACKGROUND: Management of recurrent prostate cancer (CaP) after radiotherapy (RT) is dependent on accurate localization of the site of recurrent disease. OBJECTIVE: To describe the anatomic patterns and clinical features associated with CaP recurrence following RT identified on advanced imaging. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of 184 patients with a rising prostate-specific antigen (PSA) after RT for CaP. INTERVENTION: C-11 choline positron emission tomography/computed tomography (CholPET). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Recurrence patterns were classified as pelvic soft tissue only (as a surrogate for potentially salvageable disease) versus any extrapelvic disease, and clinical features were compared between patterns. Multivariable logistic regression was used to generate a predictive nomogram for extrapelvic recurrence. Discrimination was assessed with a c-index. RESULTS AND LIMITATIONS: Recurrence site was identified in 161 (87%) patients, with 95 (59%) sites histologically confirmed. Factors associated with the detection of recurrence included the difference between PSA nadir and PSA at CholPET (odds ratio: 1.30, p<0.01) and National Comprehensive Cancer Network high-risk classification (odds ratio: 10.83, p=0.03). One hundred (54.3%) patients recurred in the pelvic soft tissue only, while 61 (33%) had extrapelvic recurrence. Of 21 patients who underwent CholPET prior to meeting the Phoenix criteria of biochemical failure, 15 (71%) had recurrence identified on CholPET with 11 localized to the pelvis. On multivariable analysis, the difference between PSA nadir and PSA at CholPET, time from RT, and National Comprehensive Cancer Network risk group were predictive of recurrence outside of the pelvis, and a nomogram was generated with a c-index of 0.79. CONCLUSIONS: CholPET identified the site of recurrence in 87% of patients with a rising PSA after RT; most commonly within the pelvis in potentially salvageable locations. A predictive nomogram was generated, and pending external validation, this may aid in assessing the risk of disease beyond the pelvis. These findings underscore the importance of advanced imaging when considering management strategies for patients with a rising PSA following primary RT. PATIENT SUMMARY: We identified anatomic patterns of recurrence in patients with a rising prostate-specific antigen after radiotherapy using C-11 choline positron emission tomography/computed tomography. Most recurrences were localized to the pelvis and we were able to generate a tool to aid in disease localization prior to evaluation with advanced imaging.

Predictors of Locoregional Failure and Impact on Overall Survival in Patients With Resected Exocrine Pancreatic Cancer.

PURPOSE: Resection of exocrine pancreatic cancer is necessary for cure, but locoregional and distant relapse is common. We evaluated our institutional experience to better understand risk factors for locoregional failure (LRF) and its impact on overall survival (OS). METHODS AND MATERIALS: We reviewed 1051 consecutive patients with nonmetastatic exocrine pancreatic cancer who underwent resection at our institution between March 1987 and January 2011. Among them, 458 had adequate follow-up and evaluation for study inclusion. All patients received adjuvant chemotherapy (n=80 [17.5%]) or chemoradiation therapy (n=378 [82.5%]). Chemotherapy and chemoradiation therapy most frequently consisted of 6 cycles of gemcitabine and 50.4 Gy in 28 fractions with concurrent 5-fluorouracil, respectively. Locoregional control (LRC) and OS were estimated with the Kaplan-Meier method. Univariate and multivariate analyses were performed with Cox proportional hazards regression models incorporating propensity score. RESULTS: Median patient age was 64.5 years (range: 29-88 years). Median follow-up for living patients was 84 months (range: 6-300 months). Extent of resection was R0 (83.8%) or R1 (16.2%). Overall crude incidence of LRF was 17% (n=79). The 5-year LRC for patients with and without radiation therapy was 80% and 68%, respectively (P=.003; hazard ratio [HR]: 0.45; 95% confidence interval [CI]: 0.28-0.76). Multivariate analysis, incorporating propensity score, indicated radiation therapy (P<.0001; HR: 0.23; 95% CI: 0.12-0.42) and positive lymph node ratio of ≥0.2 (P=.02; HR: 1.78; 95% CI: 1.10-2.9) were associated with LRC. In addition, LRF was associated with worse OS (P<.0001; HR: 5.0; 95% CI: 3.9-6.3). CONCLUSIONS: In our analysis of 458 patients with resected pancreatic cancer, positive lymph node ratio of ≥0.2 and no adjuvant chemoradiation therapy were associated with increased LRF risk. LRF was associated with poor OS. Radiation therapy should be considered as adjuvant locoregional treatment following pancreatic cancer resection.

A randomized controlled trial of bupivacaine through intracostal catheters for pain management after thoracotomy.

BACKGROUND: Optimal management of pain after thoracotomy can be challenging. Continuous infusion of local anesthetic into the incision may help reduce the amount of narcotics required to control postoperative pain. To address this issue, we performed a randomized, double-blinded, controlled trial of infusion of bupivacaine versus placebo through intercostal and subcutaneous catheters after thoracotomy. METHODS: From April 2006 to June 2007, 124 patients had intercostal catheters placed at thoracotomy and connected to continuous infusion pain pumps. Each patient had catheters placed in the intercostal space near the head of the rib and subcutaneously beneath the incision; both were connected to an infusion pump through a Y connector. Patients were randomly assigned to receive placebo (normal saline solution) or 0.25% bupivacaine as a 4 cc per hour infusion for 100 hours after thoracotomy. All personnel caring for the patients were blinded to the content of the infusion. Demographic information, visual analog pain scores, and oral morphine equivalent usage was recorded for each patient. In addition to the infusion catheters, all patients had epidural analgesia that remained in place until postoperative day 3. RESULTS: There were 60 patients in the bupivacaine arm and 64 in the placebo group. Overall mean age was 64.7 years and 65 (52.4%) were men. Mean body mass index was 28.8 kg/m(2). There were no statistical differences in any demographic parameter except that there were more men in the placebo group. Pulmonary resection was performed in 100 patients, an antireflux procedure in 16, and other miscellaneous procedures in 8. There was no statistical difference in the morphine equivalent usage between the two groups. There was also no difference between the average daily pain scores between the two groups. Length of stay was not significantly different between groups: mean (SD) of 6.2 (3.4) and 6.7 (5.0) for placebo and bupivacaine, respectively (p = 0.51). There was no operative mortality, and complications occurred in 28% of patients (placebo group, 25%; bupivacaine group, 32%; p = 0.41). CONCLUSIONS: This randomized, double-blinded, controlled trial demonstrated that the infusion of local anesthetic into the subcutaneous area and around the rib fracture site in addition to epidural analgesia did not reduce the amount of narcotic usage after a thoracotomy, nor did it affect visual analog pain scores. Pain control with intercostal catheters infusing local anesthetics did not produce a measurable pain relief beyond that provided by epidural analgesia.

Quality-of-life after total pancreatectomy: is it really that bad on long-term follow-up?

While selected pancreatic diseases may be best treated by total pancreatectomy (TP), the anticipated sequelae of pancreatic insufficiency make TP an undesirable alternative. Our aim was to determine if patients undergoing TP have a worse quality of life (QoL) than age- and gender-matched controls and poor long-term glycemic control. Ninety-nine patients undergoing TP from 1985 through 2002 were identified. The 34 survivors with no recurrent malignancy were surveyed with the Short Form-36 (SF-36), the Audit of Diabetes Dependent QoL (ADD QoL), the European Organization for Research and Treatment in Cancer Pancreas 26 (EORTC PAN 26), and our institutional questionnaire. Operative morbidity and mortality were 32% and 5%, respectively. Three late postoperative deaths (3%) were attributed to hypoglycemia. Of the 34 surviving patients, 27 (79%) agreed to participate at a mean of 7.5 years postoperatively. Seven patients had required 12 hospitalizations for poor glycemic control. Per the SF-36, two domains (role physical and general health) were decreased compared with an age- and gender-matched national population (P < .05). The ADD QoL demonstrated an overall decrease in QoL related specifically to the diabetes mellitus (P < .01), but comparison with insulin-dependent diabetics from other causes showed no significant difference in QoL. The EORTC PAN 26 instrument also showed measurable effects on QoL. Total pancreatectomy can be performed safely. QoL after TP is decreased compared with age- and gender-matched controls but not with diabetes from other causes; however, the changes are not overwhelming. TP should remain a viable option but in selected patients.

Comparison of the relative sensitivity of CT colonography and double-contrast barium enema for screen detection of colorectal polyps.

BACKGROUND & AIMS: In a population reflective of a screening setting, our aim was to compare the relative sensitivity and specificity of computed tomography (CT) colonography with double-contrast barium enema (DCBE) for detection of colorectal polyps and to assess the added value of double reading at CT colonography, using endoscopy as the arbiter. METHODS: This prospective, blinded study comprised 837 asymptomatic persons at higher than average risk for colorectal cancer who underwent CT colonography followed by same-day DCBE. Examinations with polyps > or =5 mm in diameter were referred to colonoscopy. RESULTS: CT colonography readers detected 56%-79% of polyps > or =10 mm in diameter. In comparison, the sensitivity at DCBE varied between 39% and 56% for the 31 polyps > or =1 cm. All of the readers detected more polyps at CT colonography than DCBE, but the difference was statistically significant for only a single reader (P = 0.02). Relative specificity for polyps > or =10 mm on a per-patient basis ranged from 96% to 99% at CT colonography, and 99%-100% at DCBE. Doubly read CT colonography detected significantly more polyps than DCBE (81% vs. 45% for polyps > or =1 cm [P = <0.01], and 72% vs. 44% for polyps 5-9 mm [P < or = 0.01]). CONCLUSIONS: Double-read CT colonography is significantly more sensitive in detecting polyps than single-read double contrast barium enema. DCBE was significantly more specific than CT colonography.

Colorectal cancer screening with CT colonography, colonoscopy, and double-contrast barium enema examination: prospective assessment of patient perceptions and preferences.

PURPOSE: To prospectively assess and compare perceptions of and preferences for computed tomographic (CT) colonography, colonoscopy, and double-contrast barium enema examination (DCBE) by asymptomatic patients undergoing colorectal cancer screening. MATERIALS AND METHODS: A total of 696 asymptomatic patients at higher-than-average risk undergoing colorectal cancer screening were consecutively recruited to undergo both CT colonography and colonoscopy (group 1), and a like group of 617 patients was separately recruited to undergo both CT colonography and DCBE (group 2). Standard bowel preparations were different between the groups undergoing colonoscopy and DCBE. Each patient completed a questionnaire that assessed preparation inconvenience and discomfort, examination discomfort, willingness to repeat examinations, and examination preference. Survey results were compared for significance by using the Wilcoxon rank sum or chi2 test. RESULTS: The majority of patients considered the preparation to be uncomfortable (group 1, 460 of 515 [89%]; group 2, 482 of 538 [90%]) and inconvenient (group 1, 393 of 502 [78%]; group 2, 427 of 527 [81%]). Reported discomfort was similar at CT colonography and colonoscopy (P =.63) but was less at CT colonography than at DCBE (P <.001). Patients experienced significantly less discomfort than expected at both CT colonography and colonoscopy but not at DCBE. Patients' willingness to undergo frequent rescreening was significantly greater for CT colonography than for either colonoscopy or DCBE. The acceptable time interval between screenings was significantly shorter for all examinations if the bowel preparation could be avoided. Overall, patients preferred CT colonography to colonoscopy (group 1, 72.3% vs 5.1%; P <.001) or to DCBE (group 2, 97.0% vs 0.4%; P <.001). CONCLUSION: Patients undergoing colorectal cancer screening prefer CT colonography to both colonoscopy and DCBE. The majority of patients experience discomfort and inconvenience with cathartic bowel preparation.