Thrombosis of unusual venous sites encompasses a large part of consultative hematology and is encountered routinely by practicing hematologists. Contrary to the more commonly encountered lower extremity venous thrombosis and common cardiovascular disorders, the various thromboses outlined in this review have unique presentations, pathophysiology, workup, and treatments that all hematologists should be aware of. This review attempts to outline the most up to date literature on cerebral, retinal, upper extremity, hepatic, portal, splenic, mesenteric, and renal vein thrombosis, focusing on the incidence, pathophysiology, provoking factors, and current recommended treatments for each type of unusual thrombosis to provide a useful and practical review for the hematologist. K E Y W O R D Santicoagulation, coagulation disorder, hypercoagulable, venous thrombosis

Purpose Resection of liver-only colorectal liver metastases (CRLM) with perioperative chemotherapy is potentially curative. Specific primary tumor and liver metastasis characteristics have been validated to estimate the risk of recurrence. We hypothesize that the time interval from diagnosis of CRLM to surgery, or time to surgery (TTS), is clinically prognostic. Methods Patients from a prospectively maintained institutional database at a Comprehensive Cancer Center from May 2003 to January 2018 were reviewed. Clinicopathologic, perioperative treatment, and TTS data were collected. TTS was categorized into short (< 3 months), intermediate (3-6 months), and long (> 6 months) intervals. Results Two hundred eighty-one patients were identified. While overall survival (OS) was similar across TTS, postoperative overall survival (postoperative OS) of long TTS was associated with worse survival, 44 months (95% CI, 34-52) compared to short TTS, 59 months (95% CI, 43-79), and intermediate TTS, 63 months (95% CI, 52-108), both p < 0.01. With regard to longterm OS, intermediate TTS had 5-year OS of 59% and 8-year OS of 43% compared to long TTS (5-year OS 53% and 8-year OS 18%) and short TTS (5-year OS 54% and 8-year OS 29%). Long TTS was negatively associated with postoperative OS on multivariate analysis (HR 1.6, p < 0.01) when adjusting for resection margin, CRLM size, age, and use of postoperative chemotherapy. Conclusion Short and intermediate TTS had similar survival although patients with intermediate TTS may have better odds of long-term OS. While long TTS was associated with worse survival, likely due to higher disease burden, long-term survivors were still observed.

Purpose: Preclinical data demonstrate STAT3 as an important regular in HER2+ tumors, and disruption of the IL6-JAK2-STAT-S100A8/S100A9 signaling cascade reduces HER2+ cell viability. Ruxolitinib is an FDA approved inhibitor of JAK1 and JAK2. We performed a phase I/II trial investigating the safety and e cacy of the combination of trastuzumab and ruxolitinib in patients with trastuzumab-resistant metastatic HER2+ breast cancer.Methods: Patients with metastatic HER2+ breast cancer progressing on at least 2 lines of HER2-directed therapy were eligible. The phase I portion determined the tolerable dose of ruxolitinib in combination with trastuzumab. The primary objective of the phase II was to assess the progression free survival (PFS) of the combination of ruxolitinib plus trastuzumab compared to historical control.Results: Twenty-eight patients were enrolled, with a median number of prior therapies of 4.5. Ruxolitinib 25mg twice daily was the recommended phase II dose with no DLTs. Of 26 evaluable patients in phase II, the median PFS was 8.3 weeks (95% CI: 7.1, 13.9). Among the 14 patients with measurable disease, 1 patient had a partial response and 4 patients had stable disease. Most of the adverse events were hematologic.Conclusion: While well-tolerated with a strong preclinical rationale, the combination of ruxolitinib and trastuzumab did not lead to an improvement in PFS compared to historical control in patients with trastuzumab-resistant metastatic HER2+ breast cancer.

No abstract

No abstract