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Background: Guidelines recommend the use of genomic assays such as OncotypeDx to aid in decisions regarding the use of chemotherapy for hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer. The RSClin prognostic tool integrates OncotypeDx and clinicopathologic features to predict distant recurrence and chemotherapy benefit, but further validation is needed before broad clinical adoption., Methods: This study included patients from the National Cancer Data Base (NCDB) who were diagnosed with stage I-III HR+/HER2- breast cancer from 2010 to 2020 and received adjuvant endocrine therapy with or without chemotherapy. RSClin-predicted chemotherapy benefit was stratified into low (<3% reduction in distant recurrence), intermediate (3%-5%), and high (>5%). Cox models were used to model mortality adjusted for age, comorbidity index, insurance, and race/ethnicity., Results: A total of 285,441 patients were identified for inclusion from the NCDB, with an average age of 60 years and a median follow-up of 58 months. Chemotherapy was associated with improved overall survival only for those predicted to have intermediate (adjusted hazard ratio [aHR], 0.68; 95% confidence interval [CI], 0.60-0.79) and high benefit per RSClin (aHR, 0.66; 95% CI, 0.61-0.72). Consistent benefit was seen in the subset with a low OncotypeDx score (<26) and intermediate (aHR, 0.66; 95% CI, 0.53-0.82) or high (aHR, 0.71; 95% CI, 0.58-0.86) RSClin-predicted benefit. No survival benefit with chemotherapy was seen in patients with a high OncotypeDx score (≥26) and low benefit per RSClin (aHR, 1.70; 95% CI, 0.41-6.99)., Conclusions: RSClin may identify high-risk patients who benefit from treatment intensification more accurately than OncotypeDx, and further prospective study is needed., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Importance: Approximately 25% of patients with early-stage breast cancer who receive (neo)adjuvant chemotherapy experience a recurrence within 5 years. Improvements in therapy are greatly needed., Objective: To determine if pembrolizumab plus neoadjuvant chemotherapy (NACT) in early-stage breast cancer is likely to be successful in a 300-patient, confirmatory randomized phase 3 neoadjuvant clinical trial., Design, Setting, and Participants: The I-SPY2 study is an ongoing open-label, multicenter, adaptively randomized phase 2 platform trial for high-risk, stage II/III breast cancer, evaluating multiple investigational arms in parallel. Standard NACT serves as the common control arm; investigational agent(s) are added to this backbone. Patients with ERBB2 (formerly HER2)-negative breast cancer were eligible for randomization to pembrolizumab between November 2015 and November 2016., Interventions: Participants were randomized to receive taxane- and anthracycline-based NACT with or without pembrolizumab, followed by definitive surgery., Main Outcomes and Measures: The primary end point was pathologic complete response (pCR). Secondary end points were residual cancer burden (RCB) and 3-year event-free and distant recurrence-free survival. Investigational arms graduated when demonstrating an 85% predictive probability of success in a hypothetical confirmatory phase 3 trial., Results: Of the 250 women included in the final analysis, 181 were randomized to the standard NACT control group (median [range] age, 47 [24.77] years). Sixty-nine women (median [range] age, 50 [27-71] years) were randomized to 4 cycles of pembrolizumab in combination with weekly paclitaxel followed by AC; 40 hormone receptor (HR)-positive and 29 triple-negative. Pembrolizumab graduated in all 3 biomarker signatures studied. Final estimated pCR rates, evaluated in March 2017, were 44% vs 17%, 30% vs 13%, and 60% vs 22% for pembrolizumab vs control in the ERBB2-negative, HR-positive/ERBB2-negative, and triple-negative cohorts, respectively. Pembrolizumab shifted the RCB distribution to a lower disease burden for each cohort evaluated. Adverse events included immune-related endocrinopathies, notably thyroid abnormalities (13.0%) and adrenal insufficiency (8.7%). Achieving a pCR appeared predictive of long-term outcome, where patients with pCR following pembrolizumab plus chemotherapy had high event-free survival rates (93% at 3 years with 2.8 years' median follow-up)., Conclusions and Relevance: When added to standard neoadjuvant chemotherapy, pembrolizumab more than doubled the estimated pCR rates for both HR-positive/ERBB2-negative and triple-negative breast cancer, indicating that checkpoint blockade in women with early-stage, high-risk, ERBB2-negative breast cancer is highly likely to succeed in a phase 3 trial. Pembrolizumab was the first of 10 agents to graduate in the HR-positive/ERBB2-negative signature., Trial Registration: ClinicalTrials.gov Identifier: NCT01042379.

[This corrects the article DOI: 10.1038/s41523-018-0074-6.].

Advances in the surgical management of the axilla in patients treated with neoadjuvant chemotherapy, especially those with node positive disease at diagnosis, have led to changes in practice and more judicious use of axillary lymph node dissection that may minimize morbidity from surgery. However, there is still significant confusion about how to optimally manage the axilla, resulting in variation among practices. From the viewpoint of drug development, assessment of response to neoadjuvant chemotherapy remains paramount and appropriate assessment of residual disease-the primary endpoint of many drug therapy trials in the neoadjuvant setting-is critical. Therefore decreasing the variability, especially in a multicenter clinical trial setting, and establishing a minimum standard to ensure consistency in clinical trial data, without mandating axillary lymph node dissection, for all patients is necessary. The key elements which include proper staging and identification of nodal involvement at diagnosis, and appropriately targeted management of the axilla at the time of surgical resection are presented. The following protocols have been adopted as standard procedure by the I-SPY2 trial for management of axilla in patients with node positive disease, and present a framework for prospective clinical trials and practice., Competing Interests: The authors declare no competing interests.

We examined the interaction between forphenicinol (FPL) and cyclophosphamide (CPA) or ionizing radiation (IR) on the growth of murine squamous cell carcinoma tumors SCCVII. Primary tumors were established in C3H mice by injecting SCCVII tumor cells subcutaneously into the right hind limb. FPL (100 mg/kg for 8 days) and/or CPA (25 mg/kg twice) were administered by intraperitoneal injection. Tumors were irradiated to a total dose of 40 Gy (eight 5-Gy fractions). SCCVII tumor growth was inhibited by FPL (P=0.054), IR (P=0.003) and CPA (P<0.001) compared with control. The combination of FPL and CPA inhibited tumor growth additively compared with either treatment alone in both small- and large-volume tumors. FPL did not significantly enhance the antitumor effects of IR, however, when CPA+FPL were combined with IR, significant tumor growth inhibition was observed compared with FPL alone (P<0.001), CPA alone (P=0.002) and IR alone (P=0.002). Due to its low toxicity profile, FPL may be combined with CPA, IR and other cytotoxic therapies to potentially enhance the therapeutic ratio.

Purpose: The management of unresectable locally advanced breast cancer (ULABC) remains a major challenge because of the necessity both to treat local disease and to prevent distant disease. Two consecutive Phase I/II trials of concomitant chemotherapy and radiation (CRT) were performed to attempt to address both local and distant disease control in ULABC. This analysis focuses on rates of locoregional control and radiation-associated acute and late complications., Methods and Materials: Thirty-three patients with unresectable locally advanced or inflammatory breast cancers (T4N0-3M0-1) or locally recurrent disease were treated with CRT on two consecutive Phase I/II trials. Radiotherapy consisted of 60-70 Gy to the breast or chest wall and 60 Gy to draining lymphatics in a week-on/week-off (WO/WO) schedule. Chemotherapy consisted of either continuous infusion or bolus paclitaxel +/- vinorelbine. A subset analysis of 16 patients with nonmetastatic ULABC Stage IIIB-C (T4N0-3M0) was performed. Among this cohort, 13 patients (81%) underwent planned mastectomy after CRT., Results: Of the 16 patients with Stage IIIB-C disease, acute toxicity included moist desquamation (n = 8) and Grade 3-4 neutropenia (n = 3). Late toxicity included breast reconstruction loss, decreased range of arm motion, lymphedema, and skin toxicity, although none was life-threatening. Of 15 assessable patients, 14 had a clinical response, 7 had a pathologic complete response (pCR) including 6 of 13 patients undergoing mastectomy. With a median follow-up for living patients of 43.8 months, the 4-year actuarial locoregional control, disease-free survival, and overall survival were 83%, 33%, and 56% respectively., Conclusions: Concurrent WO/WO radiation therapy and paclitaxel +/- vinorelbine is effective locoregional therapy for ULABC with an acceptable toxicity profile. Further investigation of concurrent chemoradiotherapy in ULABC is warranted.

The efficacy of replication-deficient adenoviral vectors in gene therapy is confined to the number of tumor cells the vector infects. To focus and enhance the therapeutic efficacy, we employed a conditionally replication-competent adenoviral vector with a tissue-specific promoter, DF3/MUC1, in a human esophageal adenocarcinoma model. Our results demonstrate that Ad.DF3.E1A.CMV.TNF (Ad.DF3.TNF) specifically replicates in Bic-1 (DF3-producing cells) and mediates an enhanced biologic effect due to increased TNF-alpha in the same DF3-producing cells. We also show that the increased TNF-alpha interacts with ionizing radiation to produce greater tumor regression and a greater delay in tumor regrowth in Bic-1 (DF3-producing cells) compared to Seg-1 (DF3 non-producers). Tumor cell targeting using conditionally replication-competent adenoviral vectors with tumor-specific promoters to drive viral replication and deliver TNF-alpha provides a novel approach to enhancing tumor radiosensitivity.

Background: The ability to infect tumor cells limits the antitumor effects of gene therapy. The addition of radiotherapy to treatment with Ad.Egr.TNF.11D, a replication-deficient adenovirus containing a radiation-inducible promoter, early growth response-1, and the tumor necrosis factor-alpha (TNFalpha) complementary DNA may enhance the therapeutic ratio., Methods: Seg-1 human esophageal adenocarcinoma cells were treated with Ad.Egr.TNF.11D with or without radiation. TNFalpha levels were quantified with enzyme-linked immunosorbent assay. Athymic nude mice bearing Seg-1 tumors were randomized to buffer, ionizing radiation, Ad.Egr.TNF.11D, and combination therapy. Tumor growth delay was used to compare treatment regimens. TNFalpha levels were measured in tumor homogenates and plasma., Results: Seg-1 cells treated with Ad.Egr.TNF.11D and ionizing radiation demonstrated increased TNFalpha levels at 72 hours compared with cells exposed to vector alone (124 +/- 0 pg/mL vs. 31.11 +/- 22 pg/mL; P =.008). In vivo, Ad.Egr.TNF.11D-treated tumors expressed low TNFalpha levels (151.5 +/- 107.11 pg/mg protein) compared with tumors receiving combined treatment (793.92 +/- 489.13 pg/mg protein; P =.067). Increased TNFalpha levels were associated with increased tumor growth delay after combined treatment (P <.05)., Conclusions: Radiotherapy enables focal stimulation of TNFalpha expression in Ad.Egr.TNF.11D-infected cells and thus improves local tumor control.

Hypothesis: Intraoperative quick parathyroid hormone (qPTH) monitoring and gamma probe (GP) localization greatly aid the surgeon., Design: Prospective case series of patients undergoing parathyroidectomy (PTX) with preoperative localization studies, operative data (including intraoperative qPTH values and GP localization), and outcomes. Follow-up was complete (mean, 4.2 months)., Setting: University teaching hospital., Patients: We studied 57 consecutive patients with primary hyperparathyroidism from December 1, 1999, through November 30, 2000. Of these, 51 underwent first-time PTX, and 6, reoperative PTX (rePTX)., Main Outcome Measures: Cure rate and morbidity after PTX or rePTX; sensitivity and accuracy of preoperative localization studies; prediction of cure from results of qPTH monitoring (comparing Nichols [>50% fall from the highest baseline level and lower than the lowest baseline] or normal-limit [>50% fall from first baseline level and lower than upper limit of the reference range] criteria); and value of GP localization., Results: Patients were cured in 50 (98%) of 51 PTX and 6 (100%) of 6 rePTX for single adenomas (n = 49), double adenomas (n = 4), and multigland hyperplasia (n = 3). Nichols criteria for qPTH monitoring correctly categorized 45 (92%) of 49 cured single adenomas 10 minutes after excision. Only 35 (71%) of these adenomas were correctly categorized as cured by means of the normal-limit criteria. In double adenomas, both sets of criteria in the 10-minute samples indicated unresected glands in only 2 of 4 cases. Preoperative sestamibi parathyroid scans correctly localized 38 (76%) of 50 single adenomas. The GP was used in 54 of 57 cases. All adenomas measured greater than 20% of background ex vivo, but 6 thyroid nodules also measured greater than 20% ex vivo. In double adenomas, the GP helped locate the second adenoma in only 1 of 4 cases. The GP was graded as crucial in 2 cases with dense scar (both rePTX), helpful in 12 (22%) of 54 cases (particularly in retroesophageal glands), confirmatory in 32 (59%), and not helpful in 8 (15%). The GP helped localize 3 (43%) of 7 glands not seen on sestamibi parathyroid scans., Conclusions: Intraoperative qPTH monitoring confirmed cure in most cases. For single adenomas, use of the Nichols criteria for qPTH assessment allowed more accurate and faster confirmation than the normal-limit criteria. The GP was less useful but was crucial in 2 rePTX cases; it was not specific for parathyroid tissue. Both techniques have potential pitfalls that could result in surgical failure.

Purpose: Vascular endothelial growth factor (VEGF) is an important mediator of endothelial cell proliferation and survival. The purpose of the present studies was to investigate the role of VEGF in the tumor response to ionizing radiation., Methods: Two ras-transformed murine fibrosarcoma cell lines, VEGF+/+ and VEGF-/- were exposed to ionizing radiation (0, 1, 3, 5, 7 or 9 Gy) in vitro, and clonogenic survival was determined. VEGF+/+ and VEGF-/- xenografts were generated in athymic nude mice and then treated with ionizing radiation (ten 5-Gy fractions = 50 Gy). Mean fractional tumor volume was used to evaluate treatment efficacy. To determine whether VEGF enhances tumor radioresistance by targeting endothelial cells, we performed clonogenic survival assays with human umbilical vein endothelial cells. Surviving fractions were calculated after treatment with ionizing radiation (5 Gy) and recombinant hVEGF165 (0, 1, 10, and 100 ng/mL). To determine whether VEGF neutralization enhances tumor radiosensitivity, we employed anti-VEGF165 monoclonal antibody to treat human tumor xenografts. Tumors were exposed to ionizing radiation (four 5-Gy fractions = 20 Gy) and treated with anti-VEGF antibody (0, 5, and 25 microg/kg in four intraperitoneal doses). Mean fractional tumor volume was used to evaluate treatment efficacy. To elucidate the molecular mechanism contributing to the observed anti-VEGF/ionizing radiation interaction, we exposed human umbilical vein endothelial cells to ionizing radiation (5 Gy) in the presence of anti-VEGF antibody (1 microg/mL). Sodium dodecyl sulfate polyacrylamide gel electrophoresis of cell lysates was probed for mitogen-activated protein kinase (MAPK) and MAPK kinase (MEK1/MEK2)., Results: The in vitro radiosensitivities of the VEGF+/+ and VEGF-/- clones were equivalent (D0 = 146 vs 149). However, the VEGF+/+ xenografts were more resistant to the cytotoxic effects of ionizing radiation than the VEGF-/- xenografts. VEGF+/+ xenografts demonstrated a faster doubling time (4.5 vs 6.0 days) and a shorter growth delay (15 vs 23 days) than VEGF-/- xenografts. The surviving fraction of human umbilical vein endothelial cells after exposure to ionizing radiation was significantly enhanced in the presence of VEGF (6.4% vs 12.5%). Western blot analysis demonstrated that stimulation of MAPK and MEK1/MEK2 was abrogated after exposure to anti-VEGF antibody., Discussion: These findings represent the first genetic evidence that factors other than inherent tumor cell radiosensitivity are important determinants of radiocurability. Antitumor strategies targeting VEGF and other endothelial cell survival mechanisms may be used to enhance the cytotoxic effects of radiotherapy.

Strictureplasties have proven useful and safe in Crohn's disease. Concerns have been raised, however, about the potential of carcinoma arising at the strictureplasty site. Here the authors report a case of a small-bowel adenocarcinoma developing at the site of a prior strictureplasty in a middle-aged male patient seven years postoperatively in the absence of any other preneoplastic disease of the small bowel. Presenting symptoms were of progressive obstruction after a long period of quiescent disease. With this report comes stronger evidence that adenocarcinoma does occur at strictureplasty sites, raising questions of its long-term safety.

We examined the effects of a new antiangiogenic isocoumarin, NM-3, as a radiation modifier in vitro and in vivo. The present studies demonstrate that NM-3 is cytotoxic to human umbilical vein endothelial cells (HUVECs) but not to Lewis lung carcinoma (LLC) cells nor Seg-1, esophageal adenocarcinoma cells, in clonogenic survival assays. When HUVEC cultures are treated with NM-3 combined with ionizing radiation (IR), additive cytotoxicity is observed. In addition, the combination of NM-3 and IR inhibits HUVEC migration to a greater extent than either treatment alone. The effects of treatment with NM-3 and IR were also evaluated in tumor model systems. C57BL/6 female mice bearing LLC tumors were given injections for 4 consecutive days with NM-3 (25 mg/kg/day) and treated with IR (20 Gy) for 2 consecutive days. Combined treatment with NM-3 and IR significantly reduced mean tumor volume compared with either treatment alone. An increase in local tumor control was also observed in LLC tumors in mice receiving NM-3/IR therapy. When athymic nude mice bearing Seg-1 tumor xenografts were treated with NM-3 (100 mg/kg/day for 4 days) and 20 Gy (four 5 Gy fractions), significant tumor regression was observed after combined treatment (NM-3 and IR) compared with IR alone. Importantly, no increase in systemic or local tissue toxicity was observed after combined treatment (NM-3 and IR) when compared with IR alone. The bioavailability and nontoxic profile of NM-3 suggests that the efficacy of this agent should be tested in clinical radiotherapy.

Purpose: The purpose of this study was to evaluate whether endostatin, an antiangiogenic cleavage fragment of collagen XVIII, enhances the antitumor effects of ionizing radiation (IR). Endostatin was injected to coincide with fractionated radiotherapy., Methods: Xenografts of radioresistant SQ-20B tumor cells were established in athymic nude mice. Lewis lung carcinoma cells were injected into C57BI/6 mice. Mice bearing SQ-20B xenografts were injected intraperitoneally with 2.5 mg/kg/day of murine recombinant endostatin 5 times per week for 2 weeks 3 hours before IR treatment (50 Gy total dose). Mice bearing Lewis lung carcinoma tumors were injected intraperitoneally with endostatin (2.5 mg/kg/day) four times; the first injection was given 24 hours before the first IR dose (15 Gy) and then 3 hours before IR (15 Gy/day) for 3 consecutive days. Microvascular density was assessed on tumor tissue sections by use of CD31 immunohistochemistry and light microscopy. Endothelial cell survival analyses were employed to evaluate endostatin effects on human aortic endothelial cells and human umbilical vein endothelial cells. Endothelial cell apoptosis was examined by use of FACS analysis and DAPI microscopy., Results: In SQ-20B xenografts, combined treatment with endostatin and IR produced tumor growth inhibition that was most pronounced at the nadir of regression (day 21). By day 35, tumors receiving combined treatment with endostatin and IR were 47% smaller than tumors treated with endostatin alone. Interactive cytotoxic treatment effects between endostatin and IR were also demonstrated in mice bearing Lewis lung carcinoma tumors. Significant tumor growth inhibition was observed in the endostatin/IR group at days 11 and 13 compared with IR alone. Histologic analyses demonstrated a reduction in microvascular density after combined treatment with endostatin and IR compared with endostatin treatment alone. Survival analyses confirmed interactive cytotoxicity between endostatin and IR in both human aortic endothelial cells and human umbilical vein endothelial cells but not in SQ-20B tumor cells. Combined treatment with endostatin and IR produced an increase in cow pulmonary artery endothelial apoptosis compared with either treatment alone., Discussion: The tumor regression observed after combined treatment with endostatin and IR suggests additive antitumor effects in both human and murine tumors. Importantly, the concentrations of endostatin employed produced little tumor regression when endostatin was employed as a single agent. The results from the clonogenic and apoptosis assays support the hypothesis that the endothelial compartment is the target for the endostatin/IR interaction.

The family of vascular endothelial growth factor (VEGF) proteins include potent and specific mitogens for vascular endothelial cells that function in the lation of angiogenesis Inhibition of VEGF-induced angiogenesis either by neutralizing antibodies or dominant-negative soluble receptor, blocks the growth of primary and metastatic experimental tumors Here we report that VEGF expression is induced in Lewis lung carcinomas (LLCs) both in vitro and vivo after exposure to ionizing radiation (IR) and in human tumor cell lines (Seg-1 esophageal adenocarcinoma, SQ20B squamous cell carcinoma, T98 and U87 glioblastomas, and U1 melanoma) in vitro. The biological significance of IR-induced VEGF production is supported by our finding that treatment of tumor-bearing mice (LLC, Seg-1, SQ20B, and U87) with a neutralizing antibody to VEGF-165 before irradiation is associated with a greater than additive antitumor effect. In vitro, the addition of VEGF decreases IR-induced killing of human umbilical vein endothelial cells, and the anti-VEGF treatment potentiates IR-induced lethality of human umbilical vein endothelial cells. Neither recombinant VEGF protein nor neutralizing antibody to VEGF affects the radiosensitivity of tumor cells These findings support a model in which induction of VEGF by IR contributes to the protection of tumor blood vessels from radiation-mediated cytotoxicity and thereby to tumor radioresistance.

Background: The role of "blind" thyroid lobectomy in the surgical management of patients with persistent or recurrent primary hyperparathyroidism is not known. We reviewed our experience with reoperation for hyperparathyroidism to determine the utility of blind thyroid resection in this setting., Methods: From 1982 to 1995, 269 patients underwent reoperation for hyperparathyroidism at our institution. All patients had biochemical confirmation of hyperparathyroidism and underwent noninvasive and if necessary invasive localization studies. Patients who underwent thyroid lobectomy in an attempt to extirpate the hyperfunctioning parathyroid gland form the basis of this report., Results: Thirty-two of 269 patients (12%) underwent thyroid lobectomy to remove a parathyroid gland. Intrathyroidal parathyroids were confirmed in 19 of 32 patients (59%). In 18 of 19 patients (94%), preoperative or intraoperative ultrasonography correctly identified an intrathyroidal lesion suspicious or a parathyroid. Only 1 of 6 patients (17%) undergoing a blind thyroidectomy had an intrathyroidal gland identified. Ultrasonography had a sensitivity of 95% and a negative predictive value of 99.5% in detecting an intrathyroidal parathyroid gland., Conclusions: The prevalence of an intrathyroidal parathyroid gland in our series is low (19 of 269, 7%). Ultrasonography can be used reliably to select patients for thyroid resection, reducing the need to perform a blind thyroid lobectomy and avoiding the potential morbidity of thyroid resection in this clinical setting.

Several inflammatory cytokines, most notably tumor necrosis factor (TNF) and IL-1, induce anorexia and loss of lean body mass, common manifestations of acute and chronic inflammatory conditions. In C57BL/6 female mice, the administration of TNF, IL-1, and, to a lesser extent, leukemia inhibitory factor (LIF), produced a prompt and dose-dependent increase in serum leptin levels and leptin mRNA expression in fat. IL-10, IL-4, ciliary neurotrophic factor, and IL-2, cytokines not known to induce anorexia or decrease food intake, had no effect on leptin gene expression or serum leptin levels. After administration of Escherichia coli lipopolysaccharide (LPS), leptin gene expression and leptin levels were increased. These findings suggest that leptin levels may be one mechanism by which anorexia is induced during acute inflammatory conditions.

Background: Surgical excision of gastrinomas in patients with Zollinger-Ellison syndrome (ZES) decreases the incidence of hepatic metastases, but long-term biochemical cures are achieved in fewer than 30% of cases. A growing number of patients have persistent or recurrent disease after initial operation. The effect of reoperation in these patients has not been previously reported., Methods: From December 1982 to August 1995, 120 patients with ZES underwent operation for gastrinoma resection. Seventy-eight patients had recurrent or persistent ZES after operation; 17 patients underwent 18 reoperations. After initial operation all patients underwent yearly functional and imaging studies. If a tumor was unequivocally imaged, reexploration was done., Results: Five patients, all with sporadic disease, were disease free after operation, with a median follow-up of 28 months. Tumor was found in all 18 reoperations and resected in 17. In patients with continuing disease-free intervals, locations of gastrinomas included pancreatic head lymph nodes (three), liver metastasis (one), and pancreatic tail lymph node (one). There were no deaths in the cured group; two patients in the group with persistent disease have died (median follow-up, 34 months)., Conclusions: Reoperation for gastrinoma excision resulted in elimination of disease in 30% of patients and should be considered for patients with imageable disease.

Plasma disaturated phosphatidylcholine (DSPC) concentration has been implicated as a risk factor for atherosclerosis. However, suitable methods for the estimation of these compounds in plasma are not available. In this paper, a method for the estimation of DSPC using argentation thin-layer chromatography and high-performance liquid chromatography is described. It is quantitative for the measurement of individual and total DSPC species and is not dependent on fatty acid chain length. The method employs hydrolysis of total plasma phosphatidyl choline by phospholipase C, followed by benzoylation of the diacylglycerols. The benzoates are then fractionated on silver nitrate-impregnated silica gel thin-layer chromatography plates, and the disaturated species separated and quantitated by high-performance liquid chromatography. The method is sensitive and reproducible and allows many samples to be done at once. With this method, the amounts of DSPC were found to be significantly higher in a group of normolipidemic diabetic subjects, compared to age-matched controls.