Comparison of Pheochromocytoma-Specific Morbidity and Mortality Among Adults With Bilateral Pheochromocytomas Undergoing Total Adrenalectomy vs Cortical-Sparing Adrenalectomy.

Importance: Large studies investigating long-term outcomes of patients with bilateral pheochromocytomas treated with either total or cortical-sparing adrenalectomies are needed to inform clinical management. Objective: To determine the association of total vs cortical-sparing adrenalectomy with pheochromocytoma-specific mortality, the burden of primary adrenal insufficiency after bilateral adrenalectomy, and the risk of pheochromocytoma recurrence. Design, Setting, and Participants: This cohort study used data from a multicenter consortium-based registry for 625 patients treated for bilateral pheochromocytomas between 1950 and 2018. Data were analyzed from September 1, 2018, to June 1, 2019. Exposures: Total or cortical-sparing adrenalectomy. Main Outcomes and Measures: Primary adrenal insufficiency, recurrent pheochromocytoma, and mortality. Results: Of 625 patients (300 [48%] female) with a median (interquartile range [IQR]) age of 30 (22-40) years at diagnosis, 401 (64%) were diagnosed with synchronous bilateral pheochromocytomas and 224 (36%) were diagnosed with metachronous pheochromocytomas (median [IQR] interval to second adrenalectomy, 6 [1-13] years). In 505 of 526 tested patients (96%), germline mutations were detected in the genes RET (282 patients [54%]), VHL (184 patients [35%]), and other genes (39 patients [7%]). Of 849 adrenalectomies performed in 625 patients, 324 (52%) were planned as cortical sparing and were successful in 248 of 324 patients (76.5%). Primary adrenal insufficiency occurred in all patients treated with total adrenalectomy but only in 23.5% of patients treated with attempted cortical-sparing adrenalectomy. A third of patients with adrenal insufficiency developed complications, such as adrenal crisis or iatrogenic Cushing syndrome. Of 377 patients who became steroid dependent, 67 (18%) developed at least 1 adrenal crisis and 50 (13%) developed iatrogenic Cushing syndrome during median (IQR) follow-up of 8 (3-25) years. Two patients developed recurrent pheochromocytoma in the adrenal bed despite total adrenalectomy. In contrast, 33 patients (13%) treated with successful cortical-sparing adrenalectomy developed another pheochromocytoma within the remnant adrenal after a median (IQR) of 8 (4-13) years, all of which were successfully treated with another surgery. Cortical-sparing surgery was not associated with survival. Overall survival was associated with comorbidities unrelated to pheochromocytoma: of 63 patients who died, only 3 (5%) died of metastatic pheochromocytoma. Conclusions and Relevance: Patients undergoing cortical-sparing adrenalectomy did not demonstrate decreased survival, despite development of recurrent pheochromocytoma in 13%. Cortical-sparing adrenalectomy should be considered in all patients with hereditary pheochromocytoma.

Preventive medicine of von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors.

Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10-75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2 cm; P < 0.001) and tumor volume doubling time (TVDT) was faster (22 vs 126 months; P = 0.001). All metastatic tumors were ≥2.8 cm. Codons 161 and 167 were hotspots for VHL germline mutations with enhanced risk for metastatic PanNETs. Multivariate prediction modeling disclosed maximum tumor diameter and TVDT as significant predictors for metastatic disease (positive and negative predictive values of 51% and 100% for diameter cut-off ≥2.8 cm, 44% and 91% for TVDT cut-off of ≤24 months). In 117 of 273 patients, PanNETs >1.5 cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs <2.8 cm vs ≥2.8 cm (94% vs 85% by 10 years; P = 0.020; 80% vs 50% at 10 years; P = 0.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8 cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs.

Pancreatic adenocarcinoma: Outstanding problems.

Pancreatic adenocarcinoma remains the fourth leading cause of cancer-related death and is one of the most aggressive malignant tumors with an overall 5-year survival rate of less than 4%. Surgical resection remains the only potentially curative treatment but is only possible for 15%-20% of patients with pancreatic adenocarcinoma. About 40% of patients have locally advanced nonresectable disease. In the past, determination of pancreatic cancer resectability was made at surgical exploration. The development of modern imaging techniques has allowed preoperative staging of patients. Institutions disagree about the criteria used to classify patients. Vascular invasion in pancreatic cancers plays a very important role in determining treatment and prognosis. There is no evidence-based consensus on the optimal preoperative imaging assessment of patients with suspected pancreatic cancer and a unified definition of borderline resectable pancreatic cancer is also lacking. Thus, there is much room for improvement in all aspects of treatment for pancreatic cancer. Multi-detector computed tomography has been widely accepted as the imaging technique of choice for diagnosing and staging pancreatic cancer. With improved surgical techniques and advanced perioperative management, vascular resection and reconstruction are performed more frequently; patients thought once to be unresectable are undergoing radical surgery. However, when attempting heroic surgery, a realistic approach concerning the patient's age and health status, probability of recovery after surgery, perioperative morbidity and mortality and life quality after tumor resection is necessary.

Celiaco-mesenterial arterial aberrations in patients undergoing extended pancreatic resections: correlation of CT angiography with findings at surgery.

CONTEXT: It is important to recognize arterial variants in the preoperative planning of extended pancreatic resections. The absence of surgical confirmation of radiological data is a limitation of the majority of angiographic or CT-angiographic studies of celiac and mesenteric arterial anatomy. OBJECTIVE: The purpose of this study was to test the accuracy of CT angiography in delineating the arterial architecture by comparing the resultant 3D images with findings at surgery and determining the frequency of different celiac and mesenteric arterial anatomy variants. METHODS: Abdominal CT angiographies of 350 patients were performed on a 64- and 256-MDCT scanner prior to major pancreatic or hepatobiliary surgery. Variants of celiac and mesenteric arterial anatomy were documented as 3D reconstructions. Radiological data were compared to operative photographs during extended pancreaticoduodenectomies and extended distal pancreatectomies in 59 cases. RESULTS: Only 197 patients (56.3%) had the classic arterial anatomy identified at CT angiography. The most common variants were a replaced or accessory right hepatic artery originating from the superior mesenteric artery (62 cases, 17.7%) and a replaced or accessory left hepatic artery (43 cases, 12.3%) originating from the left gastric artery. According to a comparison with operative photographs, CT angiography demonstrated 100% accuracy in identifying celiac and mesenteric arterial anatomy variants, stenoses, obstructions and aneurysms of the celiac and mesenteric branches, including those which were hemodynamically significant and which influence the choice and sequence of operative procedures. CONCLUSION: The celiac and mesenteric arterial anatomy variants are fairly common and are of great significance in planning extended pancreatic resections. Radiological findings were fully corroborated by operative data, which means that CT angiography is a reliable tool for identifying celiac and mesenteric arterial anatomy aberrations and arterial lesions.

Mechanical properties of the human gastrointestinal tract.

The tensile properties of the human esophagus, stomach, small and large bowel were examined on an Instron 1221 tensiometer. The values of maximal stress and destructive strain were the following: for esophagus-1.2 MPa and 140%, respectively, for stomach axial specimens-0.7 MPa and 190%, for stomach transversal specimens-0.5 MPa and 190%, for small bowel transversal specimens-0.9 MPa and 140% and for large bowel transversal specimens-0.9 MPa and 180%. Tests conducted on small and large bowel axial specimens permitted examination of the intestinal wall as a multi-layered structure. The mechanical properties of tested bowels in axial and transversal directions were qualitatively different. The submucosa and muscular layers condition the mechanical strength of bowel wall, while the serosa and mucosa showed no significant strength. Reproducible results were generated for cadaveric and surgically removed stomach and small intestine, which showed their mechanical properties similar under certain storage conditions. The data received could be used for monitoring of the mechanical properties of bowel wall layers under different conditions and for checking of bowel distension sequences.