Nivolumab-induced autoimmune diabetes mellitus presenting as diabetic ketoacidosis in a patient with metastatic mucosal melanoma.

INTRODUCTION: Nivolumab is an immune checkpoint inhibitor used in the treatment of several malignancies. A number of immune-related endocrinopathies have been linked to its use. CASE REPORT: We report a unique case of a 74-year-old man with well-controlled diabetes mellitus type 2 and metastatic mucosal anorectal melanoma who presented with diabetic ketoacidosis after receiving his third cycle of nivolumab 240 mg intravenous (IV) every 2 weeks. He was found to have autoantibodies against glutamic acid decarboxylase 65. Genotyping for human leukocyte antigens showed the presence of DQB1*02:01 and DRB1*03:01. MANAGEMENT AND OUTCOME: His presentation was complicated by acute renal failure. He required aggressive fluid resuscitation and insulin supplementation to reverse severe acid-base disturbance and multiple electrolyte abnormalities. After an 8-week interruption, the patient restarted nivolumab without any further evidence of adverse events over the next 12 weeks. He continues to require insulin replacement therapy. DISCUSSION AND CONCLUSION: Development of type 1 diabetes with the use of immune checkpoint inhibitors has been increasingly reported in the literature. The exact mechanism for autoimmune diabetes precipitated by nivolumab is yet to be elucidated. Patient education about the symptoms of diabetes and regular glucose monitoring cannot be overemphasized. Testing for antibodies against glutamic acid decarboxylase 65, insulin receptors, and islet cells may also prove useful. Human leukocyte antigen DQ and DR haplotyping prior to immune checkpoint inhibitor treatment might help determine susceptibility toward developing type 1 diabetes, and provide opportunities for earlier recognition, intervention, and possibly prevention.

Acquired angioedema late in the course of nivolumab treatment.

INTRODUCTION: Although programmed cell death-1 inhibitors have become the mainstay of treatment for many cancers, their use can at times be accompanied by unusual side effects. CASE REPORT: We describe herein a 43-year-old patient with Lynch syndrome and colon cancer who developed facial swelling 18 months after starting nivolumab therapy. Our patient also experienced a grade 1 maculopapular rash due to this agent. Naranjo nomogram assessment showed a probable causality between nivolumab and angioedema (score of 8). MANAGEMENT & OUTCOME: Given the modest intensity of symptoms and the excellent response of metastatic colon cancer to nivolumab, this agent was continued without interruptions. She was prescribed prednisone 20 mg orally daily as needed to be taken if the swelling progressed, or if respiratory symptoms developed. The patient experienced another two similar episodes over the next months; however, they were self-limiting and did not require steroids. Subsequently, she had no further similar symptoms. DISCUSSION: Rare reports of angioedema associated with immune checkpoint inhibitor (ICI) treatment have previously been described. The exact mechanism of these phenomena is unknown, but bradykinin release leading to increased vascular permeability might be involved. Clinicians, pharmacists, and patients should be aware of this rare side effect of ICIs as it can be life-threatening when involving the respiratory tract and causing impending airway obstruction.

KRAS-Mutated, Estrogen Receptor-Positive Low-Grade Serous Ovarian Cancer: Unraveling an Exceptional Response Mystery.

We report on a woman with aggressive estrogen receptor-positive, KRAS-mutated ovarian cancer who achieved a remarkable response to combination therapy with the MEK inhibitor (trametinib) and the aromatase inhibitor (letrozole), even though the disease had failed to respond to a combination of a PI3K inhibitor and different MEK inhibitor, as well as to trametinib and the estrogen modulator, tamoxifen, and to letrozole by itself. The mechanism of action for exceptional response was elucidated by in vitro experiments that demonstrated that the fact that tamoxifen can have an agonistic effect in addition to antagonist activity, whereas letrozole results only in estrogen depletion was crucial to the response achieved when letrozole was combined with an MEK inhibitor. Our current observations indicate that subtle variations in mechanisms of action of outwardly similar regimens may have a major impact on outcome and that such translational knowledge is critical for optimizing a precision medicine strategy. KEY POINTS: This report describes the remarkable response of a patient with KRAS-mutated, estrogen receptor-positive low-grade serous ovarian cancer treated with trametinib (MEK inhibitor) and letrozole (aromatase inhibitor), despite prior progression on similar agents including tamoxifen (estrogen modulator). In vitro investigation revealed that tamoxifen can have agonistic in addition to antagonistic effects, which could be the reason for the patient not responding to the combination of trametinib and tamoxifen. The current observations suggest that drugs with different mechanisms of action targeting the same receptor may have markedly different anticancer activity when used in combinations.

Charting a professional course for academic gynecologic oncology mentors.

OBJECTIVES: To describe the transition from a mentee to mentor role in a cohort of academic gynecologic oncologists by studying the evolution of authorship placement in peer reviewed publications by current gynecologic oncology (GO) fellowship directors. METHODS: Current GO fellowship directors were identified from the ACGME website. A Pubmed search identified all publications by all listed fellowship directors. Number of publications, and order of authorship were counted by years since medical school graduation. Milestones representing likely career transition points were developed and tracked. Descriptive statistics were used to characterize the individuals and associated institutions. Time to event curves were compared using the Kaplan Meier method. RESULTS: The study cohort comprised 58 GO fellowship program directors. The median time since medical school graduation was 22 years. Eight unique milestones reflecting the relative frequencies of authorship placement were studied. The median time to accomplishing these milestones ranged from 6 to 18 years. The timing of milestone attainment suggests a stepwise progression of events and was associated with both individual and institutional factors. CONCLUSIONS: In this cohort of 58 fellowship directors, a roadmap to mentorship was identified, that includes several measurable milestones, and representative times to attain each. Further analyses identified a set of factors associated with the rate of progression. We hope these findings can inform the evolution of mentorship in gynecologic oncology. It is possible that initiatives focused on mentorship training might include milestone tracking to facilitate development.

Practice patterns and survival in FIGO 2009 stage 3B endometrial cancer.

OBJECTIVE: To describe the practice patterns and outcomes of patients with stage 3B endometrial cancer. METHODS: We queried the National Cancer Database for all surgically staged, stage 3 patients between 2012 and 2016. Patients who received any pre-operative therapy were excluded. Demographics, tumor factors, and adjuvant therapy for the stage 3 substages were compared. Logistic regression was used to identify factors associated with adjuvant therapy. Kaplan Meier curves were generated and compared using the log-rank test. Multivariable Cox Proportional Hazards Model was used to adjust for prognostic factors. Findings with p < 0.05 were considered significant. RESULTS: Of 7363 patients with stage 3 disease, 478 (6%) had stage 3B; 1732 (23%) had stage 3A, 3457 (48%) had stage 3C1, and 1696 (23%) had stage 3C2 disease. Post-surgical treatment consisted of: combined chemotherapy (CT) and radiation (RT) (49%), CT alone (28%), RT alone (9%), 14% received no postoperative therapy. Among all stage 3 substages, patients with stage 3B disease were the least likely to receive any CT, and the most likely to receive RT alone. After adjusting for known prognostic factors, patients with stage 3A (Hazard ratio (HR) of death = 0.64) and 3C1 (HR of death = 0.79) disease had significantly worse overall survival compared to stage 3B; survival was not demonstrably different from patients with stage 3C2 disease. Patients with stage 3B disease who received CT + RT had the best overall survival. CONCLUSION: Survival of patients with stage 3B disease is similar to that of patients with para-aortic node metastases and is inferior to all others with stage 3 endometrial cancer. Less frequent CT and a higher rate of post-operative RT alone, describes a distinct practice from that seen in other stage 3 patients.

Assessment of malnutrition by unintentional weight loss and its implications on oncologic outcomes in patient with locally advanced cervical cancer receiving primary chemoradiation.

OBJECTIVES: To determine the prevalence, risk factors for, and clinical implications of unintentional weight loss on oncologic outcomes in locally advanced cervical cancer (LACC) treated with concurrent chemotherapy and contemporary radiation techniques. METHODS: This a single-institution, retrospective cohort study of patients with LACC who received definitive chemoradiation (CRT) from 2010 to 2015. Clinicopathologic factors were abstracted by chart review and characterized using descriptive statistics. Factors associated with severe weight loss (≥10% from baseline) were determined by Chi-square test. Time-to-event analysis was performed using the Kaplan Meier method and regression was performed using the Cox Proportional hazards model. RESULTS: One hundred and eight patients comprised the cohort. The majority of patients were White, obese, and had squamous histology. Almost 80% of patients experienced at least some weight loss, with 14% of patients experiencing severe weight loss. Patients with FIGO 2009 stage 3 or 4 disease had a 3.4-fold increased risk of severe weight loss compared to those with earlier stage disease. Patients who had severe weight loss had a higher risk for death (HR = 2.37, 95% confidence interval [CI] 1.77, 7.37, p = 0.036) and a trend toward high risk for recurrence (HR = 1.43, 95% CI 0.46, 3.32, p = 0.107) compared to patients without severe weight loss. CONCLUSION: Unintentional weight loss is a common symptom of patients with LACC receiving CRT that affects oncologic outcomes, yet it remains under-recognized. Increased awareness of weight loss and malnutrition may encourage interventions to improve this potentially modifiable risk factor for worse prognosis and quality of life.

HIPEC after neoadjuvant chemotherapy and interval debulking is associated with development of platinum-refractory or -resistant disease.

OBJECTIVE: To describe our single-institution oncologic outcomes of patients who received neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: We compared clinicopathologic information and outcomes for all patients with advanced stage, high-grade serous ovarian cancer who received NACT and IDS with (N = 20) or without (N = 48) HIPEC at our institution from 2010 to 2019 RESULTS: Mean age (62 years with HIPEC and 60 years without HIPEC) and proportion of stage 4 disease (40% for both) did not differ between cohorts. HIPEC patients had higher rates of complete cytoreduction (95% vs 50%), longer mean duration of surgery (530 vs. 216 min), more grade 3 or 4 postoperative complications (65% vs. 4%), and longer mean length of hospital stay (8 vs. 5 days). HIPEC patients had significantly higher risk for platinum-refractory progression or platinum-resistance recurrence (50% vs 23%; RR = 2.18; 95% CI 1.11, 4.30, p = 0.024). Median progression free survival (11.5 vs. 12 months) and all-cause mortality (19.1 vs. 30.5 months) in the HIPEC and non-HIPEC cohorts, respectively, did not differ CONCLUSIONS: HIPEC was associated with increased risk for platinum refractory or resistant disease. Higher surgical complexity may contribute to higher complication rates without improving oncologic outcomes in our patients. Further investigations and long-term follow-up are needed to assess the utility of HIPEC in primary treatment of advanced stage ovarian cancer.

Advanced uterine papillary serous cancer: Could there be a role for newer targeted therapeutic approaches or immune checkpoint inhibitors?

BACKGROUND: Although now available in oncology clinics, comprehensive germline mutation testing is being performed only in a minority of patients with advanced uterine papillary serous cancer (UPSC). Some of these patients might harbor various targetable mutations, either heritable or acquired.Data sources: We conducted a retrospective cohort study involving all consecutive patients with UPSC treated at our institution from 2009-2019. Data on epidemiology, with an accent on personal and family history of cancer, clinical presentation, disease stage, employed treatment modalities and cancer-specific survival (CSS) was sought. FINDINGS: Thirteen patients were seventy years of age or younger (≤70) while 15 were older than seventy (>70), and the two arbitrary patient cohorts were well-balanced for the TNM stage. Four UPSC patients >70 had a personal history of metachronous breast cancer. We also identified five cases of breast cancer, two cases of colon cancer, and one of each ovarian and uterine cancer in the first-degree relatives of UPSC patients >70. More than 90% of patients had surgical excision/debulking, and nearly half of the patients in each group received systemic chemotherapy. The most common chemotherapy regimen was carboplatin-paclitaxel every three weeks. Compared to patients ≤70, the UPSC patients >70 were less likely to undergo postoperative radiation therapy (6% vs 61.5%; p = 0.001) and had a worse CSS (21.8 vs. 27.4 months; HR 0.61, p = 0.03). CONCLUSIONS: Personal and family history in a cohort of older UPSC patients identified an excess of second primary cancers, and these patients displayed a shorter CSS. Comprehensive germline and tumor mutation analysis might identify optimal candidates for various targeted agents and immune checkpoint inhibitors, and ultimately improve survival. This may represent an unmet need in the UPSC patients, and further studies are needed to confirm the significance of our findings.

Rapid dissemination of practice-changing information: A longitudinal analysis of real-world rates of minimally invasive radical hysterectomy before and after presentation of the LACC trial.

OBJECTIVE: Characterize change in rates of minimally invasive (MIS) radical hysterectomy after presentation of the LACC trial. METHODS: Longitudinal analysis of data from Vizient® database for surgically treated patients with invasive cervical cancer from April 2017-March 2019. Covariates studied included patient demographic and obesity categories, dates of LACC trial presentation and publication, and hospital characteristics. RESULTS: 2102 cervical cancer patients had surgery at 201 hospitals. Most were age 31-50 (51.2%), White (64.8%), and had public (49.2%) health insurance. Annual rates of MIS fell from 51.9% to 27.1% after the LACC trial presentation (RR 0.52, 95% CI 0.47, 0.58; p < 0.0001). Adjusting for within hospital correlation, the odds of MIS dropped by 13% per month (OR = 0.872 per month, 95% CI 0.852, 0.891; p < 0.001), without further change in rates of MIS after the peer-review publication (OR = 1.033 per month, 95% CI 0.897, 1.189; p = 0.65). Rates of MIS declined across all demographics (RR = 0.32-0.65; p < 0.01), except in morbidly obese women (RR = 0.90; p = 0.60). Applying mixed effects model, rates of MIS fell by 3% per month in morbidly obese women versus 18% per month if body mass index<40 kg/m2. NCCN member hospitals and hospitals with gynecologic oncology fellowship training programs significantly reduced rates of MIS radical hysterectomy faster, but not earlier, than other hospitals. CONCLUSIONS: Rates of MIS radical hysterectomy fell dramatically and pervasively after the LACC trial presentation, despite ongoing substantive controversy. Practice pattern changes were not significant in morbidly obese women.

The elevated risk of ovarian clear cell carcinoma among Asian Pacific Islander women in the United States is not affected by birthplace.

OBJECTIVE: To determine incidence of ovarian clear cell cancer (OCCC) by race ethnicity and how that relationship is affected by birthplace among Asian Pacific Islanders (API). METHODS: The 18 registries of the U.S. Surveillance, Epidemiology, and End Results (SEER) dataset were queried to identify all women registered with epithelial ovarian cancer from 1973 to 2013. Relative risks of OCCC to non-OCCC based on ethnicity and birthplace were compared. RESULTS: We identified 72, 501 women with epithelial ovarian cancer in the dataset; of these, 5078 (7.0%) had OCCC and 4859 (6.7%) were API. The age-adjusted incidence rate/100,000 women of OCCC was significantly higher in API women (0.6, 0.5-0.6 95% CI) compared to any other ethnicity. A significantly higher proportion of API women had OCCC (14.5%) compared to their White (6.6%, RR 2.2, p < 0.0001) and Black counterparts (4.3%, RR 3.4, p < 0.0001). The majority of API women were foreign-born (70.8%). The relative risk of clear cell compared to non-clear cell epithelial ovarian cancer was not demonstrably different among foreign born API women with ovarian cancer (RR 1.1, 95% CI 0.9 to 1.3, p = 0.6). CONCLUSIONS: We have demonstrated that, in the US, there is an elevated risk of OCCC associated with API ethnicity. Place of birth does not appear to significantly modify the association, suggesting that the increased risk of OCCC in API women may not be affected by acculturation or environmental exposure. Future research exploring the complex relationships between ethnicity and risk of malignancy will be important as we make progress in understanding disease process and treatment.

Current status of hyperthermic intraperitoneal chemotherapy (HIPEC) for ovarian cancer in the United States.

OBJECTIVES: 1.) To compare frequency of HIPEC use in ovarian cancer treatment before and after publication of the phase III study by van Driel et al. in January 2018. 2.) To compare associated rates of hospital-based outcomes, including length of stay, intensive care unit (ICU) admission, complications, and costs in ovarian cancer surgery with or without HIPEC. METHODS: We queried Vizient's administrative claims database of 550 US hospitals for ovarian cancer surgeries from January 2016-January 2020 using ICD-10 diagnosis and procedure codes. Sodium thiosulfate administration was used to identify HIPEC cases according to the published protocol. Student t-tests and relative risk (RR) were used to compare continuous variables and contingency tables, respectively. RESULTS: 152 ovarian cancer patients had HIPEC at 39 hospitals, and 20,014 ovarian cancer patients had surgery without HIPEC at 256 hospitals. Following the trial publication, 97% of HIPEC cases occurred. During the index admission, HIPEC patients had longer median length of stay (8.4 vs. 5.7 days, p < 0.001) and higher percentage of ICU admissions (63.1% vs. 11.0%, p < 0.001) and complication rates (RR = 1.87, p = 0.002). Index admission direct costs ($21,825 vs. $12,038, p < 0.001) and direct cost index (observed/expected costs) (1.87 vs. 1.11, p < 0.001) were also greater in the HIPEC patients. No inpatient deaths or 30-day readmissions were identified after HIPEC. CONCLUSIONS: Use of HIPEC for ovarian cancer increased in the US after publication of a phase III clinical trial in a high-impact journal, though the absolute number of cases remains modest. Incorporation of HIPEC was associated with increased cost, hospital length of stay, ICU admission, and hospital-acquired complication rates. Further studies are needed in order to evaluate long-term outcomes, including morbidity and survival.

Severe terminal ileitis induced by single-agent nivolumab administered every four weeks.

INTRODUCTION: Use of immune checkpoint inhibitors has expanded to a variety of malignancies including hepatocellular carcinoma, where nivolumab and pembrolizumab have shown durable responses in approximately a sixth of patients. CASE REPORT: We report herein a patient with metastatic hepatocellular carcinoma who achieved a durable response to the second-line agent nivolumab administered intravenous 240 mg every two weeks. After 18 months of therapy, nivolumab schedule was changed to intravenous 480 mg every four weeks, per patient's request and for convenience of administration. Four days after this change, the patient developed severe terminal ileitis.Management and outcome: This condition was managed in hospital with intravenous steroids. The patient improved clinically and was discharged on an oral steroid taper. A month later, nivolumab was reinstated at 200 mg intravenous infusions every two weeks, without any re-occurrence of terminal ileitis to date as of six months after the probable drug reaction. DISCUSSION: To our knowledge, this is the first report of terminal ileitis with nivolumab administered every four weeks. As postmarketing evaluation of nivolumab continues, similar side effects may be observed. Prompt diagnosis and steroid therapy in these cases are imperative to ensure a favorable outcome. Resuming immunotherapy once the adverse event has resolved appears to be a safe option.

Management and clinical outcomes in uterine malignant mixed Müllerian tumor: Lessons from a single-institution series.

Malignant mixed Müllerian tumor remains an important contributor to morbidity and mortality in women with uterine cancer. Surgery is the primary treatment modality, followed by chemotherapy and/or radiation for advanced disease or high-risk patients. Clinico-epidemiologic characteristics and outcomes in older versus younger women with Malignant mixed Müllerian tumor may differ. We analyzed and now report on 15 consecutive patients with uterine Malignant mixed Müllerian tumor treated at our institution from 2000 to 2018. The mean age at diagnosis was 65 years; 60% (9/15) patients were overweight/obese. Forty-six percent (7/15) had hypercholesterolemia, an association not previously linked with Malignant mixed Müllerian tumor in the literature. All patients but one had surgical excision of the tumor. A third of patients received adjuvant radiation therapy. A majority of patients received chemotherapy; the preferred regimen was carboplatin-paclitaxel. The patients older than 70 had a tendency towards a more advanced disease stage at diagnosis and a significantly shorter cancer-specific survival than their younger counterparts (6 months vs. 102 months (hazard ratio 1.32, p = 0.02)). Our study's conclusions are restricted due to its relatively small size, retrospective design, and some variation in the chemotherapy doses administered in individual patients. Larger studies are needed to confirm the significance of our findings.

Inferior outcomes in immunocompromised Merkel cell carcinoma patients: Can they be overcome by the use of PD1/PDL1 inhibitors?

Cases of Merkel cell carcinoma have become increasingly more common in the last two decades, and its incidence has been predicted to climb further. Immunosenescence might explain in part the higher Merkel cell carcinoma prevalence in seniors aged 70 and older. This cancer might also be more aggressive in immunocompromised patients. In a subset of immunocompromised Merkel cell carcinoma patients, we identified significant lymphopenia and a more advanced disease stage compared with their immunocompetent counterparts. Time to death in this cohort was much shorter than in immunocompetent subjects, and their likelihood of death from Merkel cell carcinoma was five times higher. Avelumab approval in 2017 represents an important step forward in the therapy of Merkel cell carcinoma. Hopefully, PD1/PDL1 inhibitors will improve survival in immunocompromised Merkel cell carcinoma hosts, traditionally linked with inferior clinical outcomes.

Severe left atrial enlargement due to carfilzomib use in multiple myeloma.

Several cardiovascular effects have been attributed to carfilzomib in the recent literature. These side effects must be recognized promptly by treating physicians and pharmacists. Special attention is required in patients with pre-existing cardiac conditions, liver function abnormalities and/or advanced age. This is the first report of a severe left atrial enlargement due to carfilzomib use in the setting of multiple myeloma. This condition improved dramatically seven months after cessation of carfilzomib. The authors discuss further various cardiac and vascular abnormalities linked with carfilzomib in the medical literature. Prompt withdrawal of this agent is essential in these cases as it may prevent dismal outcomes.

Impact of therapeutic modalities on disease-specific survival in older adults with glioblastoma: A single-institution retrospective cohort study.

The standard first-line therapy for glioblastoma consists of maximal surgical resection, followed by concurrent chemoradiotherapy. Optimal management for older glioblastoma patients is unknown as they have not been extensively studied in clinical trials. We report data from a series of 156 consecutive glioblastoma patients treated at our institution from 2007 to 2017. Compared to glioblastoma patients aged 70 or less, the patients older than 70 were less likely to undergo surgical resection (34% vs. 64%; p = 0.0003), be treated with adjuvant chemotherapy (37% vs. 59%; p = 0.01) or radiation therapy (36% vs. 56%; p = 0.03). Disease-specific survival was significantly shorter in this age group (4.7 vs. 15.3 months; p = 0.002). Nonetheless, when older patients did undergo surgery or chemotherapy, the proportional improvement in cancer-specific survival was similar to the one recorded in younger patients, which is concordant with the findings of other published reports. A multidisciplinary input from neurosurgeons, medical and radiation oncologists, oncology pharmacists and geriatricians remain paramount for the optimal management of glioblastoma in patients older than 70.

Clinico-epidemiologic characteristics and patterns of care in Kaposi's sarcoma: Data from a single-institution series.

In the late 20th to early 21st century, most new Kaposi's sarcoma cases were associated with HIV coinfection and low CD4 T-cell counts. After introduction of effective antiretroviral therapy, the clinical and epidemiologic characteristics of Kaposi's sarcoma may have changed. We analyzed and now report on 27 consecutive Kaposi's sarcoma patients treated at our institution from 2007 to 2017. Most patients were HIV-positive Caucasian men on antiretroviral therapy; the average CD4 T-cell count was above the AIDS-defining level of 200 cells/mm3. Seven patients had Kaposi's sarcoma with mucosal involvement, and 20 had skin-only Kaposi's sarcoma. Mucosal Kaposi's sarcoma patients had a mean CD4 T-cell count of 83 cells/mm3 as opposed to 381 cells/mm3 for patients with skin-only involvement (p = 0.005). Survival was significantly compromised in both groups but even more so in Kaposi's sarcoma patients with mucosal involvement (306 vs. 609 days). Along with other reports, our findings suggest that Kaposi's sarcoma may develop in HIV patients in the modern era despite well-controlled HIV disease. This is significant since Kaposi's sarcoma remains an important contributor to morbidity and mortality in HIV-infected patients.

Merkel cell carcinoma: long-term follow-up of a single institution series and clinical outcomes by immunological status.

Merkel cell carcinoma (MCC) usually arises in sun-exposed areas of older patients and might be more aggressive in the immunocompromised. We performed a retrospective chart review of 40 consecutive MCC patients treated at our institution between the years 2006-2017. Clinical and epidemiologic data were utilized and therapy and survival were analyzed. Compared to Surveillance, Epidemiology, and End Results (SEER) data, our population was entirely Caucasian (100% versus 95%; P=0.11) and male predominant (75% versus 63%; P=0.11). The median age was 76. The patients more often had Tumor-Node-Metastasis (TNM) stage I disease (50% versus 39%; P=0.00003) and a primary tumor size <2cm (57.5% versus 34%; P<0.01). They received more frequently lymph node dissection (70% versus 63%, P=0.002) compared with the SEER findings. We identified a subset of immunocompromised patients (n=10) who presented with more stage III disease (40% versus 33%; P=0.021). Time to death averaged 290.1 days in this subset versus 618.2 days (P<0.001) in immunocompetent patients and their likelihood of death was 5 times higher. As clinical outcomes in MCC patients vary by immunological status, a multidisciplinary tumor-board approach may better optimize individual patient management.

Longitudinal thumbnail fissures due to erlotinib therapy for lung cancer.

While therapy with epidermal growth factor receptor inhibitors leads to meaningful clinical responses in several tumor types, it has also been linked with perplexing toxic effects. Skin effects of these agents such as generalized papulo-pustular rash, trichomegaly, fingertip fissures, xerosis, pruritus and paronichias are now well characterized. Though uncommon, nail atrophic changes have also been described in subjects treated with these classes of agents. We describe herein unusual longitudinal thumbnail fissures caused by erlotinib therapy for metastatic lung cancer. Unique features are bilateral thumbnail involvement and central location in the nail bed. This side effect of erlotinib has not been previously reported in the medical literature.

Diagnosis and treatment of Clostridium difficile (C. diff) colitis: Review of the literature and a perspective in gynecologic oncology.

Clostridium difficile infection (CDI) is a major cause of nosocomial diarrhea with the potential for significant morbidity and mortality. Colonization in a susceptible individual, with risk factors such as prior antibiotic use, advanced age, or medical comorbidities, may result in symptomatic infection. Although patients with a gynecologic malignancy may be at a higher risk of developing CDI due to an increased likelihood of having one or more risk factors, data do not consistently support the idea that chemotherapy or cancer itself are independently associated with CDI. For diagnosis of CDI, we recommended using a multi-step approach, with a highly sensitive initial rapid test such as the enzyme immunoassay (EIA) for glutamate dehydrogenase (GDH) or nucleic acid amplification testing (NAAT), followed by confirmatory testing with of the above two tests or EIA toxin A/B, which has high specificity. Treatment varies based on the severity of disease. We recommend vancomycin as first-line therapy for an initial episode of mild/moderate or severe CDI, with consideration of fidaxomicin for patients at particularly high risk for recurrence. Rectal vancomycin may play an adjunctive role for some severe cases, while surgical intervention is indicated for fulminant CDI if no improvement six or more days after initiating medical therapy. For non-severe recurrent disease, the initial treatment regimen should be repeated, while subsequent episodes are more appropriately treated with a tapered and pulsed dose of vancomycin, fidaxomicin, or fecal microbiota transplantation.