Disseminated carcinomatosis of the bone marrow caused by granulocyte colony-stimulating factor: A case report and review of literature.

BACKGROUND: Disseminated carcinomatosis of the bone marrow (DCBM) is a widespread metastasis with a hematologic disorder that is mainly caused by gastric cancer. Although it commonly occurs as a manifestation of recurrence long after curative treatment, the precise mechanism of relapse from dormant status remains unclear. Granulocyte colony-stimulating factor (G-CSF) can promote cancer progression and invasion in various cancers. However, the potential of G-CSF to trigger recurrence from a cured malignancy has not been reported. CASE SUMMARY: A 55-year-old Japanese woman was diagnosed with Ewing sarcoma localized on the fifth lumbar vertebrae 6 years after curative gastrectomy for T1 gastric cancer. After palliative surgery to release nerve compression, pathological diagnosis of the resected specimen was followed by curative radiation and chemotherapy. During treatment, G-CSF was administered 32 times for severe neutropenia prophylaxis. Eight months after completing definitive treatment, she complained of severe back pain and was diagnosed as multiple bone metastases with DCBM from gastric cancer. Despite palliative chemotherapy, she died of disseminated intravascular coagulation 13 d after the diagnosis. Immunohistochemical examination of the autopsied bone marrow confirmed a diffuse positive staining for the G-CSF receptor (G-CSFR) in the relapsed gastric cancer cell cytoplasm, whereas the primary lesion cancer cells showed negative staining for G-CSFR. In this case, G-CSF administration may have been the key trigger for the disseminated relapse of a dormant gastric cancer. CONCLUSION: When administering G-CSF to cancer survivors, recurrence of a preceding cancer should be monitored even after curative treatment.

[A Case of Advanced Squamous Cell Carcinoma of the Lung 19 Years after Chemoradiotherapy of Limited-Disease Small-Cell Lung Cancer].

A 65-year-old man was referred to our hospital because of a fever and cough 19 years after chemoradiotherapy for small-cell lung cancer(SCLC)in the right middle lobe. Computed tomography(CT)revealed a normal right middle lobe, but found pneumonia and a tumor at the bronchial entrance of the right upper lobe. After treating the pneumonia with antibiotics and prednisolone, transbronchial biopsies(TBBs)revealed the tumor to be squamous cell carcinoma(SCC). Eight lines of chemotherapy including immune checkpoint inhibitors(ICIs)were completed with a 42-month survival following the initiation of chemotherapy for SCC, after which he ultimately died of hemoptysis. Survival of over 10 years from small- cell cancer is rare. We herein report the prognosis of SCLC and the treatment of subsequent primary lung cancer.

[Electronic Reporting of PRO-CTCAE in Outpatients Receiving Chemotherapy-A Single-Center Feasibility Study].

To investigate the feasibility of utilizing electronically provided patient-reported outcomes(ePRO)to detect adverse events, we conducted a single-center prospective study targeting patients with advanced cancers who were receiving chemotherapy at our outpatient clinic. Participants were asked to respond to 71 relevant items from the PRO-CTCAE once a week for 8 consecutive weeks. An outpatient nurse evaluated the corresponding items on the CTCAE. Forty of 85 outpatients were enrolled. Thirty-four patients were excluded because of Bring Your Own Device(BYOD)restrictions and 11 were excluded for other reasons, including poor physical conditions. Those without BYOD were significantly older than the study participants(median age: 72 and 66 years, respectively)and were more likely to be male(65% and 35%, respectively). The overall response rate was 77%. The median number of symptoms per participant rated as ≥Grade 1 was 26(range: 0-48) by ePRO and 6(range: 1-15)by the nurse(p<0.01). Among the total number of symptoms detected by ePRO, the percentage of symptoms detected by both the nurse and ePRO was low(median: 4%, range: 0-67%). Symptoms detected consistently by both the nurse and ePRO were alopecia(67%), anorexia(38%), paresthesia(36%), diarrhea(28%), malaise(27%), oral mucositis(25%), constipation(24%), limb edema(24%), pain(22%), and dysgeusia(21%), suggesting that healthcare professionals tend to pay more attention to the symptoms that they think lead to intervention. Our findings indicate that the implementation of the ePRO system in outpatient care may help clinicians accurately recognize adverse events at earlier stages.

Lymphocyte-to-Monocyte Ratio Is a Predictive Biomarker of Response to Treatment with Nivolumab for Gastric Cancer.

INTRODUCTION: Patients with unresectable or recurrent gastric cancer who have an objective response (OR) to nivolumab monotherapy are expected to have a good long-term prognosis. However, the OR rate for nivolumab treatment is low at 11%, and there is a need for biomarkers to predict the treatment response. This study aimed to analyze the significance of systemic inflammation-related variables and clinicopathologic characteristics as predictive markers of response to nivolumab monotherapy in patients with advanced gastric cancer. METHODS: In this retrospective cohort study, we enrolled 71 consecutive patients who received nivolumab monotherapy for unresectable or recurrent gastric cancer. Receiver operating characteristic curve analysis was performed to determine the cutoff values of systemic inflammation-related variables, predictors of treatment response, and other prognostic factors related to nivolumab therapy. We focused on systemic inflammation-related variables measured before nivolumab induction and 2 weeks after its first administration and performed multivariate analysis to assess whether they could be used as prognostic factors. RESULTS: Multivariate analysis revealed that a lymphocyte-to-monocyte ratio (LMR) of ≤3.28 after 2 weeks of initial nivolumab treatment (2wLMR) is a statistically significant predictor of treatment response (p = 0.012). The progression-free survival (PFS) rate of patients with liver metastasis was significantly worse than that of the other patients (1-year PFS: 0.0 vs. 24.4%, respectively; p = 0.005). The overall survival (OS) of patients with a low 2wLMR was significantly longer than that in patients with a high 2wLMR (1-year OS: 37.4 vs. 18.9%, respectively; p = 0.022). CONCLUSIONS: Thus, the 2wLMR could be a useful biomarker to predict response to nivolumab treatment and the prognosis of unresectable and recurrent gastric cancer.

Efficacy of regorafenib in acute pulmonary carcinomatous lymphangitis as a manifestation of rectal cancer: A case report.

Recent therapeutic advancements have prolonged the survival duration of patients with metastatic or recurrent colorectal cancer even during salvage treatment. Although treatment with regorafenib and trifluridine/tipiracil combination has exhibited apparent survival benefits, clear and objective evidence of a response to these drugs is scarce. Herein, the present study reports the case of a patient with rectal cancer refractory to multiple surgical interventions and standard chemotherapy. Treatment with regorafenib resulted in immediate improvement of respiratory failure caused by pulmonary lymphangitic carcinomatosis. This improvement persisted for over 3 months and was confirmed by radiology. Our findings suggest that regorafenib can reduce peritumoral edema via its interaction with the vascular endothelial growth factor receptor. Thus, regorafenib functions as a multityrosine kinase inhibitor to alleviate symptoms of lymphangitic carcinomatosis despite the low potency of the drug.

[What Are Patients' Expectations from Palliative Chemotherapy ?]

BACKGROUND: The gap between patients' and physicians' expectations from treatment has been a difficult problem in oncology because it affects decision-making. This study identified patients' expectations from their treatment and concerns when palliative chemotherapy was initiated. METHODS: Patients completed a questionnaire, which included open-ended questions about their expectations from the treatment and their biggest concerns at that moment after a clear explanation that the nature of their metastatic or recurrent cancer treatment was palliative and not curative. One hundred and sixty-five consecutive Japanese patients were included in this study. RESULTS: Twenty-nine percent of the patients described their expectation as "symptomatic improvement,"28% as"objective treatment effect,"and 19%as"cure."The most common concern was the toxicity(41%). No significant change was revealed in later-line treatment. CONCLUSION: The patients' expectation from palliative chemotherapy and concerns should be considered more precisely in each phase. Dedicated palliative care and explanation of toxicity controlon the initiation of treatments are essential.

Treatment of metastatic refractory colorectal cancer following regorafenib failure.

At present, there is no set strategy for the treatment of patients with colorectal cancer subsequent to the failure of standard treatment, other than the use of regorafenib (RGR) and TAS-102. The best order in which to use these drugs, and their safety and efficacy in combination with other drugs, are currently under investigation. It has been reported that RGR has a resensitizing effect on tumors that have previously failed to respond to anticancer drugs; this makes it a promising salvage therapy for colorectal cancer. The present report describes the results of a retrospective study on 17 patients with metastatic colorectal cancer who received RGR treatment following the failure of standard therapy. Following RGR failure, 71% of the patients were fit for further anticancer treatment, and these patients survived longer than those who did not receive further treatment. Furthermore, this intervention did not shorten the period of best supportive care. As a considerable number patients were fit for further anticancer therapy after RGR treatment, which resulted in prolonged survival without shortening the period of best supportive care, it may be beneficial for future research to focus on finding the optimal time at which to switch from RGR to further anticancer therapy.

Gastrointestinal stromal tumor of the stomach with axillary lymph node metastasis: A case report.

Gastrointestinal stromal tumors (GISTs) are the most common type of gastrointestinal mesenchymal tumors, although metastasis to the perigastric lymph nodes is relatively rare, compared with liver or peritoneal metastasis. In this report, we describe a case of stomach GIST with a solitary simultaneous metastasis in the left axillary lymph node. A 68-year-old man was diagnosed with a large upper-stomach GIST, and computed tomography and positron emission tomography revealed masses in the left axilla and right mediastinum. We did not detect evidence of metastases to the liver, or other sites including the perigastric lymph nodes, although findings from the surgically resected axillary lymph nodes were compatible with GIST metastasis. Treatment using imatinib markedly reduced the gastric and mediastinal lesions, and this response persisted for 3 years. The patient subsequently experienced rapid growth of the gastric lesion without mediastinal or axilla recurrence, which required palliative surgery. Despite continuing medical treatment (sunitinib and regorafenib), the patient died of liver metastases 23 mo after the surgery. Based on our findings, it appears that the axillary lymph nodes can be a potential metastatic site for GIST metastasis.

A Case of Spontaneous Tumor Lysis Syndrome in Malignant Melanoma.

A 62-year-old man with a complaint of back pain lasting 2 months was admitted. He also presented a huge abdominal tumor. Diagnostic imaging showed metastatic tumors in the liver, lumbar vertebrae and bilateral lung. An ultrasound-guided needle biopsy revealed a lung tumor containing melanic tissue. Subsequently, there was an evident elevation in uric acid, phosphoric acid, potassium and lactate dehydrogenase concentrations in serum. Continuous hemodiafiltration and administration of rasburicase was initiated following the diagnosis of tumor lysis syndrome (TLS). However, he died on the fourth day owing to arrhythmia. An autopsy revealed metastatic deposits in the liver, lung, spine, ribs, and lymph nodes along the biliary system. Microscopic examinations revealed massive necrosis of normal hepatocytes and tumor cells with disseminated tumor thrombi in the portal system. The catastrophic progression of TLS appears to be influenced by a persistent portal blood flow deficiency by portal tumor thrombus in this case.

[A case of advanced signet ring cell carcinoma of the appendix that responded to S-1 and docetaxel].

A 68-year-old man was admitted to our hospital after testing positive in a fecal occult blood test. He was subsequently diagnosed with advanced signet ring cell carcinoma of the appendix with disseminated peritoneal disease and ascites. Weekly chemotherapy with S-1 was commenced, and after three courses, the tumor shrunk in size and the ascites decreased. Two more courses were administered;however, disease progression was noted because of increasing ascites. The chemotherapy regimen was changed to weekly docetaxel, and after two courses, further tumor shrinkage and a decrease in ascites were noted. The disease course of this patient suggests that S-1 and docetaxel were effective against signet ring cell carcinoma of the appendix. Here we report this case and discuss the relevant literature.

[A case of advanced gastric cancer with esophageal invasion treated by neoadjuvant S-1/CDDP chemotherapy].

A 75-year-old man was found, by endoscopic examination, to have type 2 advanced gastric adenocarcinoma with esophageal invasion in the cardia. Endoscopy and other modalities revealed observable esophageal invasion. To minimize surgical intervention, we treated him with S-1 and cisplatin as neoadjuvant therapy. Treatment was as follows: S-1(80mg/m2)was administered orally for 3 weeks followed by 2 weeks of rest, and cisplatin(60mg/m2)was administered by intravenous drip on day 8. Two courses of treatment resulted in marked shrinkage of the primary lesion and improvement of the esophageal invasion. Total gastrectomy with splenectomy, and D2 lymph node dissection were performed with an adequately long proximal margin, without thoracotomy. Pathological efficacy was Grade 2. At present, 1 year after the operation, the patient presents no evidence of a recurrence. We concluded that through neoadjuvant chemotherapy for advanced gastric cancer with esophageal invasion, thoracotomy could be avoided, thereby reducing risks associated with surgery.

[Successful withdrawal from disseminated intravascular coagulation caused by disseminated carcinomatosis of bone marrow originated from gastric cancer treated by sequential therapy consisting of MTX and 5-FU and palliative radiotherapy].

A 5 8-year-old man with severe back pain caused by multiple vertebral metastases developed disseminated intravascular coagulation(DIC). We adopted palliative radiotherapy(8 Gy/1 day)for palliation of his back pain as initial treatment. Afterwards, we started sequential chemotherapy consisting of methotrexate(MTX)and 5-fluorouracil(5-FU). After two courses, DIC was resolved, and the patient was discharged in fair condition after five more courses of MTX and 5-FU therapy.

[An effective case of gemcitabine therapy with post-operative peritoneal recurrence of intrahepatic cholangiocarcinoma].

The patient was a 53-year-old man who had undergone left hepatectomy due to intrahepatic cholangiocarcinoma in August 2007. Pathologically, the tumor was diagnosed as a cholangiocellular carcinoma (T2, N0, M0, Stage II). Ascites appeared about one year after surgery and control was difficult using diuretics. Since abdominal CT revealed peritoneal recurrence with massive ascites, we conducted chemotherapy using gemcitabine (GEM) in September 2008. In the outpatient setting, GEM at a dose of 1, 000 mg/body was administered once a week with a 1-week rest as 1 course. The response was assessed as a complete response (CR) because abdominal CT after 7 courses of chemotherapy showed the disappearance of both ascites and the peritoneal nodules. An adverse effect for GEM was grade 3 anemia, but we could continue the chemotherapy until September 2009. At present, CR has been observed, and one year and three months have passed since the peritoneal reccurrence.

[Survey of gemcitabine treatment for advanced pancreatic cancer in 20 hospitals of Nagano Prefecture].

To establish an effective therapy for pancreatic cancer, we made a retrospective survey of gemcitabine treatment performed at 20 hospitals in Nagano Prefecture. We analyzed data of 106 patients (64 men and 42 women, median age 66 years (33-83 years old)), half of whom had stage IV disease. Gemcitabine was administered for 3 consecutive weeks with one week rest in 57 patients, biweekly in 30 patients, initially for 3 weeks with 1 week rest and switched to biweekly schedule to 15 patients, and with another regimen to 4 patients. Analysis of the results of gemcitabine treatment between the 3 weeks with 1-week-rest regimen and the biweekly regimen revealed no differences between regimens in growth inhibition and symptom alleviation. However, we found less occurrence of blood toxicity in the biweekly regimen (40%) than in the 3 weeks with 1 week-rest regimen (59%). Median survival time for the biweekly regime was 9.7 months, only slightly longer than that of the 3 weeks with 1-week-rest regimen (8.5 months). The present study showed that a biweekly regimen for gemcitabine administration may be equivalent to the standard regime of 3 weeks with 1-week-rest regimen. Moreover, the biweekly regimen has advantages over the 3 weeks with 1-week rest regimen both economically and in terms of convenience for outpatient treatment. Therefore, the present results should be confirmed in future prospective studies, with the hope of developing a new standard treatment regimen for pancreatic cancer.

[Clinical problems in gemcitabine treatment for unresectable pancreatic cancer in the elderly--a multicentric retrospective study of 53 cases].

In Gemcitabine treatment, elderly patients with unresectable pancreatic cancer are more likely to suffer from haematological and non-haematological adverse effects than non-elderly patients. Forty percent of the elderly patients were dropped from the initial protocol due to the adverse effects, mainly because of non-haematological events or symptoms. To avoid adverse effects, the administration schedule for Gemcitabine tended to be less often and at a lower dose for elderly patients among members of the Nagano Pancreatic Cancer Study Group. However, the fact that some cases showed a limited effect from this administration schedule albeit without adverse effect, might suggest that the frequency of ordinary administration schedule should be maintained, although the Gemcitabine dose could be decreased in unresectable pancreatic cancer patients in poor condition.