Multiple Liver Metastases Research Articles

Long-term survival of pancreatic neuroendocrine tumor with multiple liver metastases treated by surgery and transcatheter arterial chemoembolization: Report of two cases

Long-term survival of pancreatic neuroendocrine tumor with multiple liver metastases treated by surgery and transcatheter arterial chemoembolization: Report of two cases

A case of effective response to Gem+nab-PTX therapy for pancreatic cancer with multiple liver metastases

A case of effective response to Gem+nab-PTX therapy for pancreatic cancer with multiple liver metastases

Abstract 2396: Heterogeneity of colorectal cancers and multiple liver metastases by mutation and copy number profiling

Abstract To investigate genetic and genomic heterogeneity in liver metastases of colorectal cancer, multiple tumor foci in the liver per patient were identified on the basis of radiological images and samples from these systematically biobanked. For a total of 67 patients, 258 metastatic tumor samples were collected (minimum of 2 and maximum of 9 samples per patient, median of 4 samples per patient). Additionally, for n = 14 patients, tumor samples from the corresponding primary colorectal cancer were also available. DNA isolated from these samples was subjected to mutation profiling by Sanger sequencing for the genes BRAF, KRAS, PIK3CA and TP53, as well as allele-specific copy number profiling by CytoscanHD SNP array. For the four genes investigated for mutations, 39/67 (58%) of the patients were homogeneous in their mutation profile, while 21/67 (32%) were heterogeneous (one or more samples had mutations not detected in all samples). For 7/67 patients (10%), no mutations were detected in any of these four genes. For 9/14 patients with matching primary tumors, there was complete concordance between the primary tumor and all liver metastases profiled for mutations, while the remaining 5/14 patients showed discordance in mutation profile between the primary tumor and at least one of the liver metastases profiled. High resolution copy number profiles of this cohort detected many of the aberrations previously described in primary colorectal cancer, specifically gain of chromosomes 7, 8q, 13q and 20q, and loss of chromosomes 5q, 8p, 15q, 17p and 18q. The extent of heterogeneity observed in patient-wise mutation profiles was largely mirrored in the copy number profiles of the same tumors. 16/27 (60%) of the patients for which both mutation and copy number profiles were available showed concordance in the degree of heterogeneity per patient. In summary, intra-individual heterogeneity varied from patient to patient, with results from the genetic and genomic data types largely concurring. Citation Format: Sharmini Alagaratnam, Tuva Høst Brunsell, Stine Aske Danielsen, Anita Sveen, Mette Eknæs, Merete Hektoen, Bård Røsok, Bjørn Atle Bjørnbeth, Arild Nesbakken, Ragnhild Lothe. Heterogeneity of colorectal cancers and multiple liver metastases by mutation and copy number profiling. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2396.

Abstract 510: A novel circulating cell free DNA-based assay in colorectal cancer patients during treatment with systematic chemotherapy

Abstract Introduction: Although circulating cell-free DNA (cfDNA) in blood plasma is being touted as a frontier noninvasive approaches, its clinical utility still remains questionable. The purpose of this study was to compare the efficacy of cfDNA by comparing blood CEA levels and radiological evaluation in patients with unresectable metastatic colorectal cancer (mCRC) who received systemic chemotherapy. Experimental Procedures: In this study, we measured aberrant cancer-specific methylation in cfDNA and the concentration of cfDNA in plasma obtained following each treatment cycle of systemic chemotherapy in three patients with mCRC. To analyze aberrant cancer-specific methylation, we used a modified highly sensitive assay for bisulfite DNA followed by fluorescence-based PCR, as reported previously (JNCI 2009). This methodology can detect methylation status in eight regions, therefore both recovery score (RS) and methylation score (MS), ranged from 0-8 at a given time. We measured RS and MS two-times in each plasma specimen obtained before administration of systemic chemotherapies. Results: In this pilot study, we examined a series of blood plasma obtained from three patients who received oxaliplatin-based chemotherapy together with molecularly-targeted agents. Despite initial tumor shrinkage in the metastases, all patients ultimately developed progressive disease (PD). Patient1 had wild-type KRAS, but had developed a sigmoid colon cancer with synchronous multiple liver and lung metastases. In contrast, Patient2 had mutant KRAS with sigmoid colon cancer and synchronous multiple liver metastasis. Both patients 1 and 2, demonstrated decreasing levels of CEA after the first-line chemotherapy, along with low methylation scores and concentration of cfDNA. Interestingly, in both patients, MS and concentration level of cfDNA increased prior to radiographic documentation of PD. Patient3 harbored BRAF V600E mutation, and a cancer in the ascending colon with systemic lymph node metastasis. Although, in this case, the tumor development progressed rapidly, similar to patients 1 and 2, MS and the concentration levels of cfDNA also increased prior to radiographic documentation of rapid PD. Conclusions: Our novel DNA methylation and concentration-based monitoring assay is a novel methodology for capturing DNA methylation in circulating cell-free DNA in plasma, and is useful for the early identification of colorectal cancer patients who are at risk of developing PD prior to radiographic documentation. Citation Format: Toshiaki Toshima, Takeshi Nagasaka, Yoshiko Mori, Takashi Kawai, Tomokazu Fuji, Fumitaka Taniguchi, Keisuke Kimura, Kazuya Yasui, Hiroyuki Kishimoto, Yuzo Umeda, Hiroshi Tazawa, Ajay Goel, Toshiyoshi Fujiwara. A novel circulating cell free DNA-based assay in colorectal cancer patients during treatment with systematic chemotherapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 510.

Abstract 3970: Impact of endoscopic stent insertion on detection of viable circulating tumor cells for obstructing colon cancer

Abstract The obstructive colorectal cancer(CRC) was reported to be 7-20% of CRC. For the patients (pts) with obstructive colorectal cancer, self-expanding metallic stents (SEMS) have been useful as a palliative treatment. Insertion of SEMS for obstructive colorectal cancer is used as a bridge to surgery approach. But suspicion have been raised about whether shear forces that act on the tumor during expansion of the stent may result in a release of cancer cells into the circulation (i.e., CTCs). This study was conducted to clarify whether insertion of colonic stents results in increased levels of viable CTCs (v-CTCs). For detecting viable CTCs(v-CTCs) of CRC, we employed a novel method, TelomeScan F35 detection system. The system was constructed with a GFP-expressing attenuated adenovirus, in which the telomerase promoter regulates viral replication. 7.5 ml of peripheral blood samples were obtained before and after stent insertion and after operation. GFP-positive and CD45-negative cells were counted as v- CTCs. This study was a single institution trial, approved by the Kure Medical Center IRB. Surgical operation was scheduled within 1 month after stenting. Between October 2013 and June 2015,10 pts aged 58-89 years (5 males and 5 females) were enrolled. The surgical operation (R0) was performed in 9 cases. CEA was reduced to <50% of baseline value in 6 of 9 measurable pts after resection. 6 pts had no v-CTCs before stenting. Among them, 3 pts had increasing number of 1-3 v-CTCs after stenting and 1 of them developed multiple liver metastasis 12 month after resection. While, 4 pts had v-CTCs (1-19 cells) before stenting and 3 of these 4 patients had significant increase of number of v-CTCs (1-21 cells) after stent insertion. 2 of them had 12 and 14 v-CTCs, respectively after operation, despite the normalized value of CEA. The present study suggested that endoscopic stent insertion may result in tumor cell dissemination into the peripheral circulation and may induce early distant metastasis. In conclusion, v-CTCs may become useful for prognosis assessment, especially when SEMS insertion is considered. Citation Format: Shinya Yamashita. Impact of endoscopic stent insertion on detection of viable circulating tumor cells for obstructing colon cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3970.

Tu1288 Gastric Cancer Patients With Multiple Liver Metastases Were Successfully Treated With Chemo-Immunotherapy Using Lentinan

Tu1288 Gastric Cancer Patients With Multiple Liver Metastases Were Successfully Treated With Chemo-Immunotherapy Using Lentinan

Simultaneous resection of synchronous colorectal liver metastases provides similar overall survival rates as delayed resection

Aims: The optimal surgical approach to synchronous colorectal liver metastases it was not standardized, yet. Although it was proved that the morbidity and mortality rates after simultaneous and delayed resection are similar, the survival rates achieved by these approaches still represent a subject of debate. This study compares the overall survival rates achieved by patients who underwent simultaneous resection or delayed resection. Methods: All the patients undergoing liver resection with curative intent, between 1995 and 2014, for liver only synchronous colorectal metastases were included in this study. The survival rates achieved by simultaneous resection and delayed resection, respectively, were compared by using Log-rank test. Results: Of 238 patients undergoing hepatectomy for synchronous colorectal metastases, 193 (81%) underwent simultaneous resection and 45 (19%) underwent delayed resection. The morbidity and mortality rates were not statistical significantly higher in patients undergoing simultaneous resection (p value > 0.05). The 1-, 3- and 5-year overall rates achieved by simultaneous resection (85.7%, 50.1% and 30.4%, respectively) were similar to those observed in delayed resection group (87.7%, 63% and 29.7%, respectively - p value = 0.817). The differences in survival rates were not statistically significant even in patients with rectal tumors (p value = 0.693), presenting locally advanced primary tumors - T3/T4 (p value = 0.957), positive lymph nodes (p value = 0.519) or more than 3 metastatic lymph nodes - N2 (p value = 0.801), multiple liver metastases (p value = 0.221), metastases larger than 5 cm (p value = 0.454), or undergoing major liver resections (p value = 0.979). Conclusions: Simultaneous resection provides similar survival rates as delayed resection, even in N-positive patients or those with primary rectal tumors, locally advanced colorectal tumors, multiple metastases or undergoing major hepatectomies.

The Surgical strategy for ruptured neuroendocrine tumor of the pancreas with multiple liver metastases

The Surgical strategy for ruptured neuroendocrine tumor of the pancreas with multiple liver metastases

Clinical effect of laparoscopic I-stage resection for colorectal liver metastasis

Objective To investigate the safety, feasibility and clinical effect of laparoscopic Ⅰ-stage resection of colorectal liver metastasis (CRLM). Methods The retrospective cohort study was adopted. The clinicopathological data of 11 patients who underwent laparoscopic Ⅰ-stage resection of CRLM at the Affiliated Tumor Hospital of Zhengzhou University from February 2012 to October 2015 were collected. The primary lesions were confirmed by preoperative colonoscopy, abdominal CT and pathological biopsy, and liver metastases were diagnosed by abdominal enhanced CT or MRI. Patients selected preoperative individualized adjuvant therapy according to their conditions, and then underwent laparoscopic Ⅰ-stage resection of CRLM. After operation, patients received adjuvant chemotherapy of FOLFOX6 (oxaliplatin+ calcium folinate+ fluorouracil) or FOLFRIRI (irinotecan+ calcium folinate+ fluorouracil) regimens. The pre-, intra- and post-operative indexes were recorded, including (1) location and diameter of tumor and preoperative treatment; (2) surgical method, volume of intraoperative blood loss, operation time, resection margin and number of lymph node dissected; (3) complications, result of pathological examination, time of gastrointestinal function recovery, time for diet intake, duration of hospital stay, adjuvant therapy and recurrence of tumor. Patients were followed up by outpatient examination and telephone interview. The regular reexaminations of tumor marker, ultrasound and abdominal CT were applied to patients for detecting the recurrence of tumor till November 2015. Measurement data with normal distribution and with skewed distribution were presented as ±s and M(range), respectively. Results (1)Preoperative indexes: ascending colon cancer was detected in 2 patients, descending colon cancer in 1 patient, sigmoid cancer in 2 patients and rectal cancer in 6 patients. There were 6 solitary liver metastases with tumor diameter of 2.0-5.0 cm and 5 multiple liver metastases with average tumor number of 2.4 and tumor diameter of 1.0-4.0 cm. Four patients underwent preoperative neoadjuvant chemotherapy and 1 with rectal cancer underwent neoadjuvant radiotherapy. (2) Intra-operative status: all the 11 patients received successful laparoscopic Ⅰ-stage resection of CRLM. Laparoscopic liver irregular wedge resection was performed in 7 patients, regular hepatic lobes resection in 4 patients, left hemicolec-tomy in 2 patients, right hemicolectomy in 2 patients, Miles operation in 4 patients and Dixon operation in 3 patients. The operation time and volume of intraoperative blood loss were (245±61)minutes and (400±277)mL, without the occurrence of uncontrollable bleeding. The distal and proximal resection margins of colorectal cancer specimens (R0 resection) and circumferential resection margin of rectal cancer were negative. The median number of lymph node dissected, positive lymph node, negative resection margin of liver tumor (R0 resection)and positive laparoscopic resection margin (R1 resection) were 16 (range, 11-27), 0 (range, 0-7), 10 and 1, respectively. (3) Postoperative status: 2 patients had postoperative complications including 1 with intra peritoneal effusion and 1 with intraperitoneal infection, without occurrence of bile leakage, abdominal bleeding, anastomotic leakage, subphrenic abscess and hepatic failure. The time of postoperative gastrointestinal function recovery, time for diet intake and duration of hospital stay were (3.0±0.6)days, (3.0±0.9)days and (11.0±4.0)days, respectively. All the 11 patients underwent adjuvant chemotherapy of FOLFOX6 regimen, and 1 of 11 patients changed FOLFOX6 regimen into FOLFRIRI regimen due to recurrence of liver metastases. All the patients were followed up for a median time of 17 months (range, 2-44 months). During the follow-up, 1 patient died of pulmonary, brain and abdominal metastases and 10 patients had survival without recurrence of tumor except 1 with recurrence of liver metastasis. Conclusion Laparoscopic Ⅰ-stage resection of CRLM is safe and feasible for eligible patients, with a satisfactory short-term outcome. Key words: Colorectal neoplasms; Liver metastases; Laparoscopy

I-stage resection of colon cancer and synchronous liver metastasis after conversion therapy

Objective To investigate the safety and clinical effect of Ⅰ-stage resection of colon cancer and synchronous liver metastasis after conversion therapy. Methods The retrospective descriptive study was adopted. The clinical data of 1 patient with sigmoid cancer with synchronous multiple liver metastases who was admitted to the Zhongshan Hospital of Fudan University in April 2013 were collected. The patient was diagnosed as sigmoid cancer with multiple lymph nodes surrounding colon and 5 metastatic lesions found in liver by preoperative imaging examination, and the maximum diameters of 2 metastatic lesions were 4.5 cm and 3.6 cm. The pathological results of colonoscopy indicated adenocarcinoma. After discussion of the multidisciplinary team, liver metastatic lesions were significantly reduced through mFOLFOX6 chemotherapy combined with bevacizumab treatment, and then patient underwent Ⅰ-stage resection of colon cancer with synchronous liver metastasis by the surgical procedures of partial hepatectomy+ 3D laparoscopy-assisted radical resection of sigmoid cancer. The patient received convention treatment of antibiotic, nutrition support therapy and mFOLFOX6 adjuvant chemo-therapy. The changes of lesions in liver and tumor markers were observed by tumor marker test, abdominal/pelvic CT and MRI in the upper abdomen after conversion therapy. The operation time, volume of intraoptrative blood loss, number of lymph nodes dissected and vital sign were observed in the operation. The liver function, time for out-off-bed activity, time to anal exsufflation, time of drainage tube removal, duration of hospital stay, complications, results of pathological examination and recurrence and metastasis of tumor were observed after operation. After discharge from hospital, the patient underwent monthly tumor marker test, B ultrasound and chest X-ray examination till January 2014 and abdominal/pelvic CT, magnetic resonance imaging (MRI) in the upper abdomen and colonoscopy every 6 months. The follow-up of outpatient examination and telephone interview was performed to detect the recurrence and metastasis of tumor up to September 2015. Results After preoperative 4-cycle chemotherapy, the diameters of 2 metastatic lesions in liver reduced to 3.2 cm and 2.0 cm, the levels of carcinoembryonic antigen(CEA) and CA19-9 (tumor marker) were reduced to 95.9 μg/L and 252.4 kU/L. The patient underwent successful Ⅰ-stage resection of colon cancer and synohronous liver metastasis. The operation time, volume of intraoperative blood loss, numbers of lymph nodes dissected and cancerous nodes were 208 minutes, 250mL, 14 and 1, respectively.The patient had no blood transfusion and metastasis, with the stable vital signs and good postoperative recovery. The levels of alanine transaminase (ALT) and aspartate transaminase (AST) were 1 147 U/L and 2 631 U/L at postoperative day 1, 101 U/L and 37 U/L at postoperative day 7, respectively. The out-off-bed activity, anal exsufflation, drainage tube removal and discharge from hospital were occurred at postoperative day 2, 3, 7 and 9, respectively. No anastomotic fistula, bleeding and infection were occurred after operation. The patient was diagnosed as with ulcerated sigmoid adenocarcinoma in T3N1cM1 stage (combining with liver metastasis). The patient received adjuvant therapy of mFOLFOX6 and oral capecitabine at postoperative day 40, and was followed up for 30 months with a good quality of life and without metastasis and recurrence. Conclusion Ⅰ-stage resection of colon cancer with synohronous liver metastasis can be used for initial unresectable colon cancer with liver metastasis after conversion therapy, and it is safe and feasible, with a good therapeutic effect. Key words: Colonic neoplasms, lower; Liver metastases, synchronous; Conversion therapy; One-stage resection; Laparoscopy

Preoperative CT versus diffusion weighted magnetic resonance imaging of the liver in patients with rectal cancer; a prospective randomized trial.

Introduction. Colorectal cancer is one of the most frequent cancers in the world and liver metastases are seen in up to 19% of patients with colorectal cancers. Detection of liver metastases is not only vital for sufficient treatment and survival, but also for a better estimation of prognosis. The aim of this study was to evaluate the feasibility of diffusion weighted MRI of the liver as part of a combined MR evaluation of patients with rectal cancers and compare it with the standard preoperative evaluation of the liver with CT.Methods. Consecutive patients diagnosed with rectal cancers were asked to participate in the study. Preoperative CT and diffusion weighted MR (DWMR) were compared to contrast enhanced laparoscopic ultrasound (CELUS).Results. A total of 35 patients were included, 15 patients in Group-1 having the standard CT evaluation of the liver and 20 patients in Group-2 having the standard CT evaluation of the liver and DWMR of the liver. Compared with CELUS, the per-patient sensitivity/specificity was 50/100% for CT, and for DWMR: 100/94% and 100/100% for Reader 1 and 2, respectively. The per-lesion sensitivity of CT and DWMR were 17% and 89%, respectively compared with CELUS. Furthermore, one patient had non-resectable metastases after DWMR despite being diagnosed with resectable metastases after CT. Another patient was diagnosed with multiple liver metastases during CELUS, despite a negative CT-scan.Discussion. DWMR is feasible for preoperative evaluation of liver metastases. The current standard preoperative evaluation with CT-scan results in disadvantages like missed metastases and futile operations. We recommend that patients with rectal cancer, who are scheduled for MR of the rectum, should have a DWMR of the liver performed at the same time.

Liver Resection for Metastatic Disease; A Population-Based Analysis of Trends

Objective: The study aims to evaluate all patients who underwent liver resection for metastatic disease for demographics, characteristics of the primary tumor and metastasis, volume of liver resection specimens per pathology laboratory and to describe trends in surgical treatment. Methods: Data were prospectively collected using the Dutch nationwide pathology network. All pathology reports containing details on liver resections for metastatic disease between January 2001 and December 2010 were evaluated. Results: A total of 3,916 liver resections were performed in 3,699 patients with a median age of 63 years (range 1-91). The primary tumor was mainly colorectal (n = 3,256; 88.0%). The number of ‘high volume liver centers' increased from 2 to 12 in the study period, whereas the number of ‘low volume centers' decreased. The number of liver resections increased from 224 to 596 per year (p ≤ 0.0001). A significant increase was demonstrated in elderly patients, patients with multiple metastases, liver resections for smaller metastases and minor liver resections. Conclusion: Although the majority of patients were young and had solitary metastasis, indications for liver resection are expanding as indicated by increasing numbers of elderly and patients with multiple liver metastases. Patients with non-colorectal liver metastases were seldom candidates for resection.

A Case of Sigmoid Colon Cancer in which Somatic Pain was Rapidly Alleviated after Panitumumab Administration Despite Tumor Progression

We present a 72-year-old woman with sigmoid colon cancer in whom the somatic pain was alleviated rapidly after the administration of anti-epidermal growth factor antibodies. Our patient had received 4 cycles of FOLFIRI therapy (irinotecan, 5-fluorouracil, and leucovorin) in combination with panitumumab (Pmab) for the treatment of unresectable primary cancer accompanied with multiple liver metastases and peritonitis carcinomatosa. As grade 3 paronychia eventually occurred, chemotherapy was stopped. After recovery of the grade 3 paronychia, Pmab was re-introduced and administered every alternate cycle to reduce the extent of adverse events. The patient had complained of somatic pain in the lower right abdomen just before re-initiating Pmab administration. The pain intensity decreased immediately after the administration of Pmab. On the next day her pain had remarkably alleviated and she was free from pain for a week. This phenomenon was repeatedly observed. After the re-introduction of Pmab, tumor response was evaluated on computed tomography, which showed progressive disease. We demonstrated that Pmab was effective in the alleviation of somatic pain, although the size of the tumors gradually increased.

Poster Presentation on Adrenal, Pituitary, and Other Endocrine Glands, Parathyroid Gland, Thyroid Gland

ABSTRACT BACKGROUND AND AIMS Gastrointestinal and pancreatic neuroendocrine tumors (NET) are classified as low grade (G1), intermediate grade (G2), and high grade (G3) by mitotic rate and/or Ki-67 index. The basic treatment for neuroendocrine carcinoma (NEC, G3) with remote metastasis is platinum-based systemic chemotherapy. In contrast, for patients with NET G1 or G2 with remote metastasis, multidisciplinary treatment is necessary in order to prolong patients' survival and relieve symptoms. We report here a patient with pancreatic G1 gastrinoma and its multiple liver metastases. METHODS The patient was a 42 years old male who had been suffering from diarrhea for 2 years, and his serum level of gastrin was as high as 4200 pg/mL before treatment. Needle biopsy of the liver proved the tumor was positive for chromogranin A, gastrin, and somatostatin receptor type 2A. RESULTS First, we chose an induction drug therapy with sunitinib and octreotide. The size of the liver tumors decreased dramatically and the serum gastrin level became lower than 500 pg/mL. About 1 year after diagnosis, we performed distal pancreatectomy and right hepatic lobectomy. After surgery, the serum gastrin level was normalized, and the activity of daily living (ADL) of the patient was much improved by the consecutive therapies. During the 2-year postoperative follow-up time, the course was favorable and no recurrent lesion was found. CONCLUSION Even when there are remote metastases, multidisciplinary treatment including surgical resection should be considered for G1/ G2 NET. Further, it should be necessary to study in a larger number of patients if perioperative drug therapy for G1/G2 NET with remote metastases is effective.

化学療法と二期的切除によりR0を得たS状結腸癌多発肝転移の1例

化学療法と二期的切除によりR0を得たS状結腸癌多発肝転移の1例

Adjusted Multidisciplinary Treatment Against Multiple Colorectal Liver Metastasis May Expand Indication of Intensive Treatment to Previously Excluded Elderly Patients

Colorectal carcinoma (CRC) is one of the most common causes of cancer-related mortalities, and liver metastases comprise the most frequently encountered distant metastases, which generally occur synchronously and metachronously with the rate of 10% and 15%, respectively. Recent development of various less invasive therapeutic approach against CRC, including laparoscopic operative procedures, radiofrequency ablation, and modified chemotherapy regimen not only improve the patients’ quality of life and survival, but also expand indication of intensive treatment to previously excluded elderly patients with reduced performance status. We focused on the feasibility and current status of adjusted multidisciplinary approach to multiple CRC liver metastases through a successfully treated elderly case with reduced performance status.

Evan's Syndrome Associated with Pembrolizumab Therapy in Metastatic Non-Small Cell Lung Cancer

IntroductionPembrolizumab is a humanized monoclonal antibody that disrupts programmed cell death 1 (PD-1) receptor signaling and unmasks native cytotoxic T-cell activity against tumor cells. Early clinical trials show that pembrolizumab induces a prolonged and sometimes dramatic antitumor response in advanced melanoma, renal cell carcinoma, and non-small cell lung cancer (NSCLC) (Topalian et al., 2012; NEJM: 366;26). Consequences of immunomodulation include immunopathologies of skin, endocrine, and/or gastrointestinal organs (Patnaik et al., 2015; Clin Cancer Res: 21;15). Herein we describe the first reported case of Evan's syndrome following the use of pembrolizumab.CaseA 67-year old man with 70-pack year smoking history presented to hospital with right-sided weakness and gait ataxia. Radiologic studies of head, thorax, abdomen, and limbs revealed left-sided frontal lobe mass, pulmonary lesions, multiple liver metastases, and left lower extremity venous thrombosis. The patient underwent cranial metastasectomy, which confirmed NSCLC primary neoplasm, followed by cranial irradiation, dexamethasone treatment, and indefinite enoxaparin. First and second-line chemotherapy with gemcitabine-carboplatin and pemetrexed failed to control his disease; he was therefore enrolled in the MK 3475-001 clinical trial and received investigational pembrolizumab (10mg/kg every 2 weeks).Following 4 cycles of pembrolizumab therapy, repeat CT scans showed a marked reduction in cerebral, liver, and lung tumor burden. Treatment continued with transient interruption of therapy at cycle 8 due to delayed side effects of cranial radiation. An additional 10 cycles (18 cycles total) of therapy were delivered, after which the patient was admitted to hospital for new-onset fatigue, exertional dyspnea, and jaundice. Laboratory evaluation showed a hemoglobin of 6.2 g/dL, reticulocyte count 239 ×103/µL, and platelet count 113 × 103/µL, with elevated total bilirubin of 1 mg/dL, LDH 398 U/L, haptoglobin level less than 20 mg/dL, and normal creatinine and liver enzymes. Peripheral blood film revealed microspherocytes and thrombocytopenia, indirect and direct testing revealed a pan-reactive IgG autoantibody, while serologic testing was negative for infectious and rheumatologic diseases. Diagnosis of warm-autoimmune hemolytic anemia was made and the patient was initiated on prednisone, azathioprine, cyclophosphamide, and IVIG therapy in conjunction with erythropoietin injections and transfusion support. Hemoglobin reached a nadir of 3.2 g/dL before recovering to 11.6 g/dL at 2 weeks into admission, followed by discharge on daily oral prednisone at 105 mg and cyclophosphamide 100 mg.Sustained hematologic stability permitted gradual prednisone taper to a dose of 20 mg. Fourteen weeks post-admission, the patient returned to hospital with severe bruising and epistaxis. Laboratory evaluation showed hemoglobin of 11.6 g/dL and platelet count of 6 × 109/L, concerning for ITP and fulfilling criteria for Evan's syndrome. Salvage therapy commenced with weekly rituximab and re-initiation of high-dose prednisone, until platelets recovered to 146 × 109/L following the fourth/final dose of rituximab. Prednisone taper was re-trialed with complete discontinuation of steroids after 24 weeks. Despite a persistently positive Coombs test, the patient maintained normal hemoglobin and platelet counts 40 weeks after rituximab therapy. Opportunistic Aspergillus fumigatus pulmonary infection followed salvage therapy, but was successfully treated with voriconazole over 12 weeks. CT staging scans at 48 weeks post-discontinuation of pembrolizumab demonstrated stable metastatic disease.ConclusionReversal of cancer-induced immune suppression through PD-1 inhibition has the potential to provoke immunodysregulation against multiple hematologic lineages. Though autoimmune hyperactivation persists for months after pembrolizumab cessation, immune-related hemolysis and thrombocytopenia remain amenable to treatment with corticosteroids and rituximab. Despite immune downregulation with corticosteroids and rituximab, pembrolizumab appears to exhibit sustained immune control over advanced malignancy in this case. [Display omitted] [Display omitted] DisclosuresOff Label Use: Rituximab to treat refractory ITP. Butler:Merck: Consultancy.

Endometrioid Adenocarcinoma Arising From Adenomyosis in a Premenopausal Woman: A Case Report

Endometrioid adenocarcinoma derived from adenomyosis is rare. A premenopausal woman, aged 36, was referred to us for evaluation of multiple solid tumors in the pelvis. MRI revealed multiple tumors in uterine myometrium and omentum. Their T2 and enhanced T1-weighted imaging led us to a diagnosis of uterine sarcoma. Hysterectomy with bilateral salpingo-oophorectomy, omentectomy, and pelvic lymphadenectomy was performed. Histopathology revealed grade 3 endometrioid adenocarcinoma with squamous differentiation. Cancer nests were observed adjacent to the adenomyotic foci. Postoperative classification was pT3aN1M1. Rejecting adjuvant therapy, the patient died 16 days later from rapid enlargement and rupture of the metastasized liver and respiratory failure. An autopsy revealed mass lesions in the pelvic cavity and compressed small intestines causing ileus. Bone metastasis, multiple lymph node metastases including para-aortic, and lung metastases were also revealed. Multiple liver metastases had caused biliary obstruction and hepatic failure. The tumor-induced hypercoagulable condition resulted in multiple thromboses, which in turn led to hemorrhaging in the lungs and eventual respiratory failure. Histological examination of the pelvic mass lesions revealed mainly poorly differentiated carcinoma. The tumor cells contained bizarre nuclei and exhibited high mitotic activity. This case was high-potential malignant tumor as the tumor rapidly grew and infiltrated multiple organs in a short period. It was a type II carcinoma with biologically aggressive behavior. J Med Cases. 2015;6(12):554-558 doi: http://dx.doi.org/10.14740/jmc2357e

P3-6-5 - An investigation about the efficacy of measuring serum CA 19-9 in patients with advanced urothelial carcinoma

Background: The present study was undertaken to investigate whether serum levels of carbohydrate antigen (CA) 19-9 is effective for predicting prognosis in patients with advanced urothelial carcinoma (UC). Methods: Patients diagnosed as locally advanced or metastatic or recurrent UC in our department between Apr 2008 to Oct 2014 were evaluated retrospectively. Pathological TNM stage was showed if patients underwent radical surgery, and clinical TNM stage was showed if not. Metastatic disease was defined as positive for extra-regional lymph node metastasis or metastasis in other organs. CA 19-9 was assayed with ELISA reader for all cases and expressed in U/ml with 30 U/ml taken as the cut-off upper value for normal. One-way analysis of variance and Student's or Welch's t-test were used for comparative data analysis. Kaplan-Meier method and log-rank test were used to compare survival time. Results: Out of 40 cases enrolled, 7 patients who showed a low value in serum CA 19-9 (<= 2 U/ml) were eliminated because they were highly suspected of Lewis A negative blood type. Two patients in advanced state with multiple liver metastases were also eliminated. Median follow-up time was 12 months. The mean values of CA 19-9 was 36.6 U/ml. The values in serum CA 19-9 were not significantly different among three types of UC. The percentage of rise in CA 19-9 for >= T3 tumors was significantly high when compared to <= T2 tumors (p = 0.034). Conversely, the percentage of rise in CA 19-9 for metastatic disease was not significantly high when compared to non-metastatic disease (p = 0.276). T stage and metastatic state did not correlate with prognosis except DSS in metastatic disease (p = 0.014), however, patiens with high serum CA 19-9 levels demonstrated significantly better prognosis in DSS and OS than that of low levels (p = 0.022, p = 0.019, respectively). Conclusion: Patients of advanced urothelial carcinoma with high serum CA 19-9 levels may predict good prognosis.

A 5-year recurrence-free survivor with over ten colorectal liver metastases undergoing FOLFOX plus bevacizumab followed by two-stage hepatectomy.

A 62-year-old male was admitted because of lower left abdominal pain and diarrhea. The patient was diagnosed with rectal cancer and multiple liver metastases. First, the laparoscopic Hartmann operation with a D3 lymph node dissection was performed. After five cycles of folinic acid, 5-fluorouracil and oxaliplatin (FOLFOX) and bevacizumab, and one additional FOLFOX, the tumor markers dramatically decreased; with carcinoembryonic antigen levels ranging from 1096.3 to 7.6 ng/ml and carbohydrate antigen 19–9 levels ranging from 3248.0 to 42.1 U/ml. Computed tomography showed a bilateral 14 colorectal liver metastases which indicated stable disease by the Response Evaluation Criteria In Solid Tumors (RECIST) criteria and optimal morphologic response. A two-stage hepatectomy was performed to complete a curative resection because of the insufficient remnant liver volume. Five partial hepatic resections in the left liver and the right portal vein ligation were performed during the first operation. Thirty-four days later, a right hepatectomy was successfully performed. Pathologically, there was tumor necrosis in 90 percent of the area of the metastasized liver, and viable cells were detected in only a marginal part of the liver. The patient had an uneventful postoperative course and was discharged fifteen days after the second operation. Uracil-tegafur plus leucovorin was administered for 6 months as an adjuvant chemotherapy treatment. The patient is currently alive and has remained disease-free for more than 5 years. In conclusion, an ideal combination of perioperative chemotherapy and curative resection may provide a chance of long-term survival without recurrence of disease for selected patients with more than ten bilateral colorectal liver metastases.