Insulinoma presenting with post-prandial hypoglycaemia following fundoplication

Summary

Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an uncommon and challenging case of insulinoma soon after upper gastrointestinal surgery. A 63-year-old man presented with 6 months of post-prandial hypoglycaemia beginning after a laparoscopic revision of Toupet fundoplication. Hyperinsulinaemic hypoglycaemia was confirmed during a spontaneous episode and in a mixed-meal test. Localisation studies including magnetic resonance imaging (MRI), endoscopic ultrasound (EUS) and gallium dotatate positron emission tomography (⁶⁸Ga Dotatate PET) were consistent with a small insulinoma in the mid-body of the pancreas. The lesion was excised and histopathology was confirmed a localised well-differentiated neuroendocrine pancreatic neoplasm. There have been no significant episodes of hypoglycaemia since. This case highlights several key points. Insulinoma should be sought in proven post-prandial hyperinsulinaemic hypoglycaemia – even in the absence of fasting hypoglycaemia. The use of nuclear imaging targeting somatostatin and GLP1 receptors has improved accuracy of localisation. Despite these advances, accurate surgical resection can remain challenging.

Learning points:

Hypoglycaemia is defined by Whipple's triad and can be provoked by fasting or mixed-meal tests.

Although uncommon, insulinomas can present with post-prandial hypoglycaemia.

In hypoglycaemia following gastrointestinal surgery (i.e. bariatric surgery or less commonly Nissen fundoplication) dumping syndrome or non-insulinoma pancreatogenous hypoglycaemia syndrome (NIPHS) should be considered.

Improved imaging techniques including MRI, endoscopic ultrasound and functional nuclear medicine scans aid localisation of insulinomas.

Despite advances in imaging and surgical techniques, accurate resection of insulinomas remains challenging.

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Insulinoma presenting with post-prandial hypoglycaemia following fundoplication

Summary

Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an uncommon and challenging case of insulinoma soon after upper gastrointestinal surgery. A 63-year-old man presented with 6 months of post-prandial hypoglycaemia beginning after a laparoscopic revision of Toupet fundoplication. Hyperinsulinaemic hypoglycaemia was confirmed during a spontaneous episode and in a mixed-meal test. Localisation studies including magnetic resonance imaging (MRI), endoscopic ultrasound (EUS) and gallium dotatate positron emission tomography (⁶⁸Ga Dotatate PET) were consistent with a small insulinoma in the mid-body of the pancreas. The lesion was excised and histopathology was confirmed a localised well-differentiated neuroendocrine pancreatic neoplasm. There have been no significant episodes of hypoglycaemia since. This case highlights several key points. Insulinoma should be sought in proven post-prandial hyperinsulinaemic hypoglycaemia – even in the absence of fasting hypoglycaemia. The use of nuclear imaging targeting somatostatin and GLP1 receptors has improved accuracy of localisation. Despite these advances, accurate surgical resection can remain challenging.

Learning points:

Hypoglycaemia is defined by Whipple's triad and can be provoked by fasting or mixed-meal tests.

Although uncommon, insulinomas can present with post-prandial hypoglycaemia.

In hypoglycaemia following gastrointestinal surgery (i.e. bariatric surgery or less commonly Nissen fundoplication) dumping syndrome or non-insulinoma pancreatogenous hypoglycaemia syndrome (NIPHS) should be considered.

Improved imaging techniques including MRI, endoscopic ultrasound and functional nuclear medicine scans aid localisation of insulinomas.

Despite advances in imaging and surgical techniques, accurate resection of insulinomas remains challenging.

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Decision tree analysis to stratify risk of de novo non-melanoma skin cancer following liver transplantation

Abstract

Purpose

Non-melanoma skin cancer (NMSC) is the most common de novo malignancy in liver transplant (LT) recipients; it behaves more aggressively and it increases mortality. We used decision tree analysis to develop a tool to stratify and quantify risk of NMSC in LT recipients.

Methods

We performed Cox regression analysis to identify which predictive variables to enter into the decision tree analysis. Data were from the Organ Procurement Transplant Network (OPTN) STAR files of September 2016 (n = 102984).

Results

NMSC developed in 4556 of the 105984 recipients, a mean of 5.6 years after transplant. The 5/10/20-year rates of NMSC were 2.9/6.3/13.5%, respectively. Cox regression identified male gender, Caucasian race, age, body mass index (BMI) at LT, and sirolimus use as key predictive or protective factors for NMSC. These factors were entered into a decision tree analysis. The final tree stratified non-Caucasians as low risk (0.8%), and Caucasian males > 47 years, BMI < 40 who did not receive sirolimus, as high risk (7.3% cumulative incidence of NMSC). The predictions in the derivation set were almost identical to those in the validation set (r² = 0.971, p < 0.0001). Cumulative incidence of NMSC in low, moderate and high risk groups at 5/10/20 year was 0.5/1.2/3.3, 2.1/4.8/11.7 and 5.6/11.6/23.1% (p < 0.0001).

Conclusions

The decision tree model accurately stratifies the risk of developing NMSC in the long-term after LT.

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Transforming growth factor beta 1 (TGFβ1) polymorphisms and haplotype structures have dual roles in breast cancer pathogenesis

Abstract

Purpose

Despite the documented dual role of TGFβ1 in breast cancer (BC) pathogenesis, the subtype-specific influences of its polymorphisms remain undocumented. The present study investigated the effects of the TGFB1 promoter region (rs1800468 or G-800A and rs1800469 or C-509T) and signal peptide (rs1800470 or C29T and rs1800471 or G74C) single nucleotide polymorphisms (SNPs) and their haplotype structures on the susceptibility and clinicopathological presentation of BC subtypes.

Methods

TGFB1 genotypes were assessed by PCR-RFLP and haplotype structures were inferred for 323 BC patients and 405 neoplasia-free women, and case–control analyses were performed by logistic regression adjusted by age. Clinicopathological parameters (age at diagnosis, tumor size, histopathological grade, lymph node metastasis, proliferation index and disease stage) were tested for correlation with TGFB1 variants. All statistical analyses were two-tailed with an alpha level of 0.05.

Results

Variants related to increased TGFβ1 production (C-509T SNP and GTCG haplotype) were associated with increased susceptibility to HER2⁺ tumors and correlated with worse prognostic parameters in HER2⁺ and triple-negative (TN) BCs, but correlated negatively to Ki67 in ER/PR⁺HER2⁻ tumors. Conversely, low TGFβ1 production variants (C29T SNP and GCTG haplotype) were protective against HER2⁺ tumors and correlated negatively with prognostic parameters in HER2⁺ and TN BCs, while indicating higher proliferation rates in ER/PR⁺HER2⁻ tumors. Furthermore, the GCCG haplotype was associated with decreased susceptibility to ER/PR⁺HER2⁻ tumors, but correlated positively with Ki67 in this subgroup.

Conclusion

The present study indicates that TGFB1 variants have subtype-specific roles in BC and may switch from tumor suppressor to promoter during tumor development, consistent with TGFβ1 dual role in BC pathogenesis.

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Decision tree analysis to stratify risk of de novo non-melanoma skin cancer following liver transplantation

Abstract

Purpose

Non-melanoma skin cancer (NMSC) is the most common de novo malignancy in liver transplant (LT) recipients; it behaves more aggressively and it increases mortality. We used decision tree analysis to develop a tool to stratify and quantify risk of NMSC in LT recipients.

Methods

We performed Cox regression analysis to identify which predictive variables to enter into the decision tree analysis. Data were from the Organ Procurement Transplant Network (OPTN) STAR files of September 2016 (n = 102984).

Results

NMSC developed in 4556 of the 105984 recipients, a mean of 5.6 years after transplant. The 5/10/20-year rates of NMSC were 2.9/6.3/13.5%, respectively. Cox regression identified male gender, Caucasian race, age, body mass index (BMI) at LT, and sirolimus use as key predictive or protective factors for NMSC. These factors were entered into a decision tree analysis. The final tree stratified non-Caucasians as low risk (0.8%), and Caucasian males > 47 years, BMI < 40 who did not receive sirolimus, as high risk (7.3% cumulative incidence of NMSC). The predictions in the derivation set were almost identical to those in the validation set (r² = 0.971, p < 0.0001). Cumulative incidence of NMSC in low, moderate and high risk groups at 5/10/20 year was 0.5/1.2/3.3, 2.1/4.8/11.7 and 5.6/11.6/23.1% (p < 0.0001).

Conclusions

The decision tree model accurately stratifies the risk of developing NMSC in the long-term after LT.

http://ift.tt/2G7N711

Transforming growth factor beta 1 (TGFβ1) polymorphisms and haplotype structures have dual roles in breast cancer pathogenesis

Abstract

Purpose

Despite the documented dual role of TGFβ1 in breast cancer (BC) pathogenesis, the subtype-specific influences of its polymorphisms remain undocumented. The present study investigated the effects of the TGFB1 promoter region (rs1800468 or G-800A and rs1800469 or C-509T) and signal peptide (rs1800470 or C29T and rs1800471 or G74C) single nucleotide polymorphisms (SNPs) and their haplotype structures on the susceptibility and clinicopathological presentation of BC subtypes.

Methods

TGFB1 genotypes were assessed by PCR-RFLP and haplotype structures were inferred for 323 BC patients and 405 neoplasia-free women, and case–control analyses were performed by logistic regression adjusted by age. Clinicopathological parameters (age at diagnosis, tumor size, histopathological grade, lymph node metastasis, proliferation index and disease stage) were tested for correlation with TGFB1 variants. All statistical analyses were two-tailed with an alpha level of 0.05.

Results

Variants related to increased TGFβ1 production (C-509T SNP and GTCG haplotype) were associated with increased susceptibility to HER2⁺ tumors and correlated with worse prognostic parameters in HER2⁺ and triple-negative (TN) BCs, but correlated negatively to Ki67 in ER/PR⁺HER2⁻ tumors. Conversely, low TGFβ1 production variants (C29T SNP and GCTG haplotype) were protective against HER2⁺ tumors and correlated negatively with prognostic parameters in HER2⁺ and TN BCs, while indicating higher proliferation rates in ER/PR⁺HER2⁻ tumors. Furthermore, the GCCG haplotype was associated with decreased susceptibility to ER/PR⁺HER2⁻ tumors, but correlated positively with Ki67 in this subgroup.

Conclusion

The present study indicates that TGFB1 variants have subtype-specific roles in BC and may switch from tumor suppressor to promoter during tumor development, consistent with TGFβ1 dual role in BC pathogenesis.

http://ift.tt/2n1KNQw

Androgen Therapy for Acute Myeloid and Hairy Cell Leukemia

Opinion statement

The purpose of this paper is to review the preclinical and clinical rationale for androgen therapy of acute myeloid (AML) and hairy cell leukemia (HCL). A major recent positive study should renew interest in this therapy, which has been reported to be effective in these leukemias for more than 50 years. Hopefully, renewed interest in this approach, which seems promising, will lead to well-designed modern studies that will precisely define a role for androgens in these leukemias. A recent large prospective, randomized study has demonstrated enhanced survival for elderly AML patients who present with WBC counts < 30,000/μL have improved overall survival when androgens are given post-remission, and numerous case reports suggest that androgens frequently restore normal peripheral blood counts in severely pancytopenic patients with HCL. Well-designed prospective studies are needed to precisely define which patients are most likely to benefit from androgen therapy and where in the treatment plan they should be incorporated.

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