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Background Diabetes mellitus (DM) is a prognostic factor for some malignancies, but its clinical implications in metastatic colorectal cancer (mCRC) patients are less clear. Therefore, we conducted a retrospective study to evaluate the impact of pre-existing type 2 diabetes mellitus (T2DM) on the survival outcomes of patients with newly diagnosed mCRC. Methodology We retrospectively included patients with newly diagnosed mCRC between January 2017 and June 2021 and with pre-existing T2DM. Data on the characteristics of patients, clinicopathological features, and drug exposure were collected from the electronic medical records. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS) and treatment-related adverse events (TRAEs). Results Among 187 mCRC patients, 54 (28.8%) had T2DM. The median follow-up was 25 months. We observed 150 OS events and 168 PFS events. Diabetes significantly and negatively impacted PFS and OS. The median for PFS (mPFS) was eight and 16 months for T2DM and no T2DM patients, respectively (p < 0.0001; log-rank test). The median overall survival (mOS) was 15 and 29 months for T2DM and no T2DM patients, respectively (p < 0.0001; log-rank test). Patients with diabetes were more often overweight or obese (59.3% vs. 24.8%; p < 0.01) and had a poorer performance status (53.7% vs. 21.1% with Eastern Cooperative Oncology Group Performance Status 1; p < 0.01). Additionally, T2DM patients had more high-risk pathological features, including G3 grading tumors (27.7% vs. 12.0%; p = 0.01), lymph node involvement (p < 0.01), BRAF-mutated (35.1% vs. 6.8%; p < 0.01), and right-sided CRC (63.0% vs. 30.1%; p < 0.01). We found no statistically significant differences in TRAEs. Nevertheless, a significantly higher rate of grade 2-4 peripheral neuropathy (22.2% vs. 5.3%; p < 0.01) was reported in T2DM patients. Conclusions T2DM is a negative prognostic factor for survival in mCRC. The paper provides empirical evidence in favor of the joint control of both pathologies. Further research is needed to establish the robustness of our results.
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Neutropenia is amongst the rare, but potentially life-threatening complications of immune checkpoint inhibitors (ICI). Awareness about this dangerous toxicity and its adequate treatment since early detection is of utmost importance. Unfortunately, there are no therapeutical guidelines to deal with neutropenia specifically. The best alternative is informed extrapolations based on reported neutropenia cases and established guidelines for other immune-related adverse events. We report a case of pembrolizumab-related grade 4 neutropenia in a patient with metastatic bladder cancer. She was successfully treated with immunosuppressive and supportive measures. Further studies are required to understand the range of immune-related adverse events and to improve their management.
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Introduction In clinical practice, there is a binary distinction between human epidermal growth factor receptor 2 (HER2)-positive and HER2-negative (HER2-) breast cancer (BC). However, within HER2- disease, there is significant heterogeneity. Particularly, HER2- tumors that express some level of HER2 by immunohistochemistry (IHC) score 1+ or 2+/in situ hybridization (ISH) non-amplified are currently defined as HER2-low. This subgroup has shown distinct biological features compared to HER2-zero (HER2-0) BC and additionally novel antibody-drug conjugate therapies have demonstrated a potential and promising activity in HER2-low BC population. This study aims to evaluate the impact of HER2-low status in response to neoadjuvant chemotherapy (NACT) in HER2- BC being HER2-low and HER2-0 status. Materials and methods In a single institution, we retrospectively reviewed clinical and pathological data of HER2 early-stage BC patients treated with NACT following definitive surgery from January 2015 to December 2020. Tumors with HER2 IHC 0 were classified as HER2-0 and IHC score 1+ and 2+/ISH non-amplified as HER2-low. The primary objective was to evaluate the rate of pathological complete response (pCR) using the definition of ypT0/Tis ypN0 according to HER2-low and HER2-0 subgroups. Secondary objectives were to evaluate biological features between the two subgroups, disease-free survival (DFS), and overall survival (OS). Pearson chi-square, Fisher's exact, and Mann-Whitney tests were performed. The Kaplan-Meier method was used to plot DFS and OS curves. A p-value of <0.05 was considered statistically significant. Results A total of 72 patients with HER2 BC were included with a median age at diagnosis of 52.5 years and a median follow-up time of 35.5 months. Of patients, 56.9% had HER2-low disease and 43.1% had HER2-0 disease. Significant differences between the two subgroups were detected regarding hormonal receptor status and proliferation grade (Ki67). In the HER2-low subgroup, 70% of tumors were luminal-like and 64.5% of HER2-0 patients had triple-negative BC (p = 0.03). There were statistically significant differences regarding estrogen (p = 0.00) and progesterone (p = 0.02) receptors. The median Ki67 rate was higher in the HER2-0 subset (mean rank = 43.9) compared to HER2-low (mean rank = 30.9) and this difference was statistically significant (p = 0.00). HER2-low patients presented more stage III tumors (65.9%) and HER2-0 patients were mainly stage II (61.3%), and this was statistically relevant (p = 0.03). The prevalence of other clinical and pathological features was comparable between both groups. HER2-low subgroup achieved lower pCR rates (14.6% vs. 29.0%) but this difference was not statistically significant (p = 0.15). Similarly, there was no difference between the two subgroups regarding DFS (p = 0.97) and OS (p = 0.35), although the data were immature. Conclusion As in prior studies, this study did not support a significant impact of HER2-low status on response to NACT in HER2- patients with early-stage BC. HER2-low patients had a lower pCR, which may suggest a worse response to classic chemotherapy regimen and may have clinical implications that should be further exploited. The prevalence of hormonal receptors in HER2-low tumors was consistent with previous data in the literature. Although retrospective, the data suggest that HER2-low tumors should be regarded as a distinct biological subtype and more research is warranted.
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Prostate cancer is the second most frequent malignancy in men worldwide and the fifth leading cause of death. Dermatomyositis (DM) is a rare idiopathic inflammatory myopathy characterized by musculocutaneous manifestations. However, DM can also present as a paraneoplastic syndrome of an underlying neoplasm. We report a case of a 65-year-old man diagnosed with prostate adenocarcinoma in the setting of severe dysphagia, muscle weakness and a facial erythematous rash. At first, the DM-related symptoms resolved with the initial treatment for the underlying malignancy. Yet, they flared up as the tumor progressed. To sum up, DM is a rare systemic disorder with unknown etiology. There is a well-established association between DM and malignancy. Malignancy-headed therapy can improve DM manifestations and the recurrence of DM symptoms may act as an early warning of malignancy relapse.
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Drug-induced liver injury (DILI) has a relatively low incidence, and as it is a diagnosis of exclusion, it can become quite a challenge for the clinician. Amoxicillin/clavulanate continues to be one of the most prescribed antibiotics and only rarely causes liver injury. We report a case of DILI associated with this antibiotic to bring attention to a rare side effect of a very commonly prescribed drug. This is the case of a 71-year-old man, with no relevant past medical history, who presented to the Emergency Department due to jaundice in the previous two weeks, with no immediate identifiable cause. The patient was admitted to our Internal Medicine Ward, and after getting a detailed clinical history and excluding other common and severe causes of liver injury, the diagnosis was made that liver injury was due to amoxicillin/clavulanate intake, thus demonstrating the importance of an in-depth history.
