Peritoneal metastases from primary appendiceal and colorectal carcinomas demonstrate distinct molecular identities on comprehensive tumor analysis.

BACKGROUND AND OBJECTIVES: Published data comparing peritoneal metastases from appendiceal cancers (pAC) and colorectal cancers (pCRC) remain sparse. We compared pAC and pCRC using comprehensive tumor profiling (CTP). METHODS: CTP was performed, including next-generation sequencing and analysis of copy number variation (CNV), microsatellite instability (MSI) and tumor mutational burden (TMB). RESULTS: One hundred thirty-six pAC and 348 pCRC samples underwent CTP. The cohorts' age and gender were similar. pCRC demonstrated increased pathogenic variants (PATHs) in APC (48% vs. 3%, p < 0.01), ARID1A (12% vs. 2%, p < 0.01), BRAF (12% vs. 2%, p < 0.01), FBXW7 (7% vs. 2%, p < 0.01), KRAS (52% vs. 41%, p < 0.05), PIK3CA (15% vs. 2%, p < 0.01), and TP53 (53% vs. 23%, p < 0.01), and decreased PATHs in GNAS (8% vs. 31%, p < 0.01). There was no difference in CNV, fusion rate, or MSI. Median TMB was higher in pCRC (5.8 vs. 5.0 mutations per megabase, p = 0.0007). Rates of TMB-high tumors were similar (pAC 2.1% vs. pCRC 9.0%, p = 0.1957). pCRC had significantly more TMB-high tumors at lower thresholds. CONCLUSIONS: Despite a reduced overall TMB, pAC demonstrated mutations distinct from those seen in pCRC. These may serve as discrete biomarkers for future study.

Evolution and Current Status of the Multidisciplinary Management of Locally Advanced Rectal Cancer.

The management of locally advanced rectal cancer has grown in both complexity and quality since the first proctectomy. What once was a malignancy with a fairly consistent treatment algorithm for decades, a recent paradigm shift in the care of these patients has led to a more personalized, multidisciplinary approach with variations in timing, sequence, duration, and potential exclusion of multimodality therapies. This review summarizes the most important evidence behind these developing overarching concepts to provide a context for this paradigm shift.

Implications of Conversion during Attempted Minimally Invasive Adrenalectomy for Adrenocortical Carcinoma.

BACKGROUND: Although advocated by some, minimally invasive adrenalectomy (MIA) for adrenocortical carcinoma (ACC) is controversial. Moreover, the oncologic implications for patients requiring conversion to an open procedure during attempted MIA for ACC are not extensively reported. PATIENTS AND METHODS: The National Cancer Database was queried for patients undergoing resection for ACC. Overall survival (OS) for patients undergoing successful MIA was compared with those requiring conversion, and additionally evaluated with a multivariable Cox regression analysis including other factors associated with OS. After propensity matching, those experiencing conversion were further compared with patients who underwent planned open resection. RESULTS: Among 196 patients undergoing attempted MIA for ACC, 38 (19.4%) required conversion. Independent of 90-day postoperative mortality, conversion was associated with significantly reduced OS compared with successful MIA (median 27.9 months versus not reached, p = 0.002). Even for tumors confined to the adrenal, conversion was associated with worse median OS compared with successful MIA (median 34.2 months versus not reached, p = 0.003). After propensity matching for clinicopathologic covariates to establish well-balanced cohorts (N = 38 per group), patients requiring conversion during MIA had significantly worse OS than those having planned open resection (27.9 months versus 50.5 months, p = 0.020). On multivariable analysis for predictors of OS, conversion during MIA (HR 2.32, p = 0.003) was independently associated with mortality. CONCLUSIONS: ACC is a rare tumor for which adequate oncologic resection is the only chance for cure. Given the relatively high rate of conversion and its associated inferior survival, open resection should be considered standard of care for known or suspected ACC.

Critical analysis of lymph node examination in patients undergoing curative-intent resection for adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare tumor and the role of lymph node dissection remains ill-defined. This study evaluates the effect of nodal examination on prognosis and survival in patients undergoing curative-intent resection of ACC. METHODS: The National Cancer Database (2004-2015) was queried for patients undergoing margin-negative resection for ACC. Patients with distant metastases, neoadjuvant therapy, multivisceral resection and T4 tumors were excluded. RESULTS: Among 897 patients, 147 (16.4%) had lymph nodes examined. Factors associated with lymph node examination included increasing tumor size (P < .001), extra-adrenal extension (P < .001), open operation (P < .001), and resection at an academic facility (P = .003). Lymph node metastasis was significantly associated with extra-adrenal tumor extension (P = .04). Lymph node harvest, regardless of the number of nodes examined, was not associated with a survival benefit. Median overall survival was incrementally worse with increasing number of positive lymph nodes (88.2 months for N0, 34.9 months for 1-3 positive nodes, and 15.6 months for ≥4 positive nodes, P < .001). CONCLUSIONS: Lymph node harvest and lymph node metastasis were associated with more advanced tumors. Although nodal harvest did not offer a survival advantage, stratifying the nodal staging classification may provide important prognostic information.

Comprehensive tumor profiling reveals unique molecular differences between peritoneal metastases and primary colorectal adenocarcinoma.

BACKGROUND AND OBJECTIVES: Peritoneal metastases (PM) from primary colorectal cancer (pCRC) are associated with poor outcomes; however, molecular differences are not well defined. METHODS: We compared unpaired tumor profiles of patients with pCRC and PM from Caris Life Sciences. Testing included next-generation sequencing of 592 genes, microsatellite instability (MSI) and tumor mutational burden (TMB). Mutations were test-defined as pathogenic (PATH). RESULTS: Six hundred seventeen pCRC and 348 PM patients had similar gender (55% male) and age (median 59). PATHs were similar between PM and pCRC in KRAS, BRAF, SMAD2, SMAD4, and PTEN. pCRC PATHs were increased in APC (76% vs 48%, P < .01), ARID1A (29% vs 12%, P < .05), TP53 (72% vs 53%, P < .01), PIK3CA (22% vs 15%, P < .05), and FBXW7 (13% vs 7%, P < .01) compared with PM. Mucinous PM had more PATHs in GNAS (19% vs 8%, P = .032) while nonmucinous PM had more PATHs in BRAF (13% vs 8%, P = .027). Right-sided PM had decreased PATHs in APC (39% vs 68%, P < .0001), ARID1A (7% vs 38%, P < .004), and TP53 (48% vs 65%, P = .033) while there were no difference for left-sided PM. Nine percent of pCRC and 6% of PM were MSI-high (P = NS). There was no difference in TMB-high, TMB-intermediate, or TMB-low between PM and pCRC. CONCLUSIONS: PM have similar rates of KRAS mutation with increased PATHs in GNAS (mucinous) and BRAF (nonmucinous) compared to pCRC. No differences in MSI or TMB were identified between PM and pCRC tumors. These findings inform future study into the molecular profile of PM.

Colorectal Cancer in the Adolescent and Young Adult Population.

Colorectal cancer in the young adult population is of increasing incidence and concern. Genetic predisposition and heritable syndromes contribute to this trend, but perhaps more concerning is the majority of new diagnoses that involve no traceable genetic risk factors. Prevention and early recognition, with a high suspicion in the symptomatic young adult, are critical in attenuating recent trends. Clinical management requires coordinated multidisciplinary care from diagnosis to surveillance in order to ensure appropriate management. This review provides a summary of key aspects related to colorectal cancer in adolescents and young adults, including epidemiology, biology, genetics, clinical management, and prevention.

Spontaneous reduction of acute cecal herniation through the foramen of Winslow.

This is the case of a 70-year-old woman who presented to the emergency department complaining of 2 hours of acute-onset epigastric pain. She had experienced this pain once before which had spontaneously resolved. Axial imaging demonstrated the cecum in an abnormal position within the lesser sac, as well as compression of the inferior vena cava and portal vein. She was taken emergently to the operating room for laparotomy, where a free-floating cecum and ascending colon was identified without ischemia, and a right hemicolectomy was performed. Foramen of Winslow hernias are rare internal hernias with a high rate of strangulation and bowel ischemia, requiring urgent surgical intervention. Operative treatment depends on the type of herniated viscera. Spontaneous reduction is not well documented.

Surgical interns: Preparedness for opioid prescribing before and after a training intervention.

INTRODUCTION: Exposure to pain management curriculum in medical school is currently variable. This paper reports on formal prescribing education, self-perceived prescribing readiness, and prescribing practices among incoming surgical residents before and after a pain management training session. METHODS: Pre-residency survey of thirty surgical interns at a single urban medical center, followed by a repeat survey after an educational session on prescription writing and opioid abuse. RESULTS: Thirty-three percent of respondents had formal education on prescription writing in medical school. Median subjective preparedness to write an opioid prescription was 1.5 (range 1-10) on a 1-10 Likert scale. Ranges of morphine milligram equivalents (MME) prescribed varied from 420-2700 MME for 8 mock surgical scenarios. Post-training, median subjective preparedness increased to 3.5 (range 1-6) and prescription accuracy (the inclusion of a medication, dose, frequency, and duration) improved from 75% to 97% (p < 0.001). Overall, 90% of interns found the training session useful. CONCLUSION: Most surgical interns were not trained in prescribing narcotics in medical school. Improved pain management curriculum is necessary to assure safe and consistent opioid prescriptions.

Three-region perfusion strategy for aortic arch reconstruction in the Norwood.

We describe a new method of selective regional perfusion during arch reconstruction in the Norwood procedure. The strategy involves direct sequential perfusion of the coronary and splanchnic circulations coupled with continuous cerebral perfusion, while repairing the arch in a distal to proximal fashion. This technique provides the potential for decreased coronary and splanchnic ischemic times, which in combination with continuous selective cerebral perfusion may further allow for warmer operating temperatures and decreased overall bypass times.

Lateral tunnel Fontan in the current era: is it still a good option?

BACKGROUND: Construction of a total cavopulmonary anastomosis using an intra-atrial lateral tunnel Fontan (LTF) is known to yield good early and midterm results. Given the current controversy regarding indications for a total extracardiac conduit Fontan, we reviewed the long-term outcomes after a LTF operation and compared them with recently published series using one or both techniques. METHODS: Between 1992 and 2008, 220 of 280 patients (median age, 2.5 years; range, 1 to 45) with a wide range of underlying diagnoses underwent a fenestrated or nonfenestrated LTF operation at our institution. Current follow-up information was available for 215 patients (98%; mean follow-up, 6.7 +/- 3.9 years). Risk factor analysis included patient-related and procedure-related variables, with death, failure (takedown or transplantation), and bradyarrhythmia or tachyarrhythmia as outcome variables. RESULTS: There was 1 early death, 10 late deaths, 3 takedown operations, and 1 heart transplantation. Kaplan-Meier estimated survival was 96% at 5 years and 95% at 10 and 15 years, and freedom from failure was 94% at 5 years and 93% at 10 years. Freedom from new supraventricular tachyarrhythmia was 98% at 5 years and 95% at 10 years; freedom from new bradyarrhythmia was 97% at 5 years and 96% at 10 years. Six patients have protein-losing enteropathy, and 2 of 6 have had Fontan takedown. Multivariable risk factors for development of supraventricular tachyarrhythmia included atrioventricular valve abnormalities (p = 0.02), and preoperative bradyarrhythmia (p = 0.01). Risk factors for bradyarrhythmia included the need for early postoperative pacing (p = 0.001). None of the patient-related variables significantly influenced survival. CONCLUSIONS: The LTF operation results in excellent midterm outcome even when used in patients with complex anatomy. The incidence of postoperative atrial tachyarrhythmia is low and depends largely on the underlying cardiac morphology and incidence of preoperative arrhythmia. The good midterm outcome after a LTF operation should serve as a basis for comparison with other surgical alternatives to complete the Fontan circulation.