Analysis of the risk factors for osteoporosis and its prevalence after gastrectomy for gastric cancer in older patients: a prospective study.

PURPOSE: Osteoporosis leads to fragility fractures and is a major public health problem. We conducted this study to analyze the prevalence of and risk factors for osteoporosis after gastrectomy in older patients. METHODS: This multicenter prospective trial comprised older patients without recurrence of gastric cancer for > 3 years after curative surgery. The prevalence of osteoporosis was identified using the World Health Organization bone mineral density (BMD)-based definition. Univariate and multivariate analyses were performed to identify the risk factors for osteoporosis. RESULTS: BMD values were measured in 267 of the 271 enrolled patients. The prevalence of osteoporosis was 38.2% (men 24.0%; women 60%). Analysis using FRAX® revealed that 51.7% of patients were candidates for pharmacologic therapy. Female sex (odds ratio [OR] 5.16, 95% confidence interval [CI] 2.61-10.2), age (OR 1.06, 95% CI 1.00-1.12), low body mass index (< 19.0 kg/m2) after gastrectomy (OR 5.31, 95% CI 2.79-10.13), and history of fracture (OR 2.06, 95% CI 1.06-4.02) were independently associated with osteoporosis. CONCLUSIONS: The prevalence of osteoporosis in older patients after gastrectomy was 38.2%. Moreover, female sex, age, low body mass index after gastrectomy, and a history of fracture were risk factors significantly associated with osteoporosis. Thus, older patients undergoing gastrectomy should have proactive surveillance and receive treatment for osteoporosis.

[A Case of Achieving CR through Chemoradiotherapy for Postoperative Oligo Lymph Node Metastasis in Gastric Cancer].

We present a case of oligo lymph node metastasis in a 70s man who had previously undergone subtotal gastrectomy for advanced gastric cancer in the prepylorus. Postoperatively, adjuvant chemotherapy was administered for a duration of 1 year. During the third postoperative year, elevated tumor markers and lymph node enlargement prompted a diagnosis of lymph node metastasis. Subsequent chemoradiotherapy resulted in a complete response(CR), which has been sustained for 2 years without any recurrence. The outcomes of this case indicate that chemoradiotherapy stands as a viable treatment option for oligo lymphatic recurrence in gastric cancer.

Docetaxel plus S-1 versus cisplatin plus S-1 in unresectable gastric cancer without measurable lesions: a randomized phase II trial (HERBIS-3).

BACKGROUND: Cisplatin plus S-1 (CS) is the standard first-line chemotherapy for advanced gastric cancer (AGC) in Japan. A previous phase III trial showed that docetaxel plus S-1 (DS) was effective for AGC without measurable lesions, but no studies have compared these two regimens. METHODS: Eligible patients had unresectable or recurrent HER2-negative AGC without measurable lesions. Patients were randomized to DS (docetaxel 40 mg/m2 on day 1, S-1 80-120 mg on days 1-14, every 3 weeks) or CS (cisplatin 60 mg/m2 on day 8, S-1 80-120 mg on days 1-21, every 5 weeks). The primary endpoint was overall survival (OS). RESULTS: All patients had unresectable primary disease. Sixty-one patients were randomly assigned to DS (n = 30) or CS (n = 31). One CS patient was ineligible due to HER2 positivity. The median number of cycles was 9.5 (range 2-49) with DS and 5.5 (range 1-10) with CS. There were no treatment-related deaths. The most common grade 3-4 non-hematological toxicity was fatigue (7% with DS, 13% with CS), followed by anorexia (3% with DS, 10% with CS) and diarrhea (3% with DS, 10% with CS). The 2-year OS rates were 43.3% with DS and 30.0% with CS (log-rank P = 0.113), with a hazard ratio of 0.617 (95% confidence interval 0.337-1.128), indicating non-inferiority of DS to CS with respect to OS (P < 0.001). CONCLUSIONS: DS showed slightly but nonsignificantly less toxicity and higher efficacy than CS for AGC without measurable lesions. DS should be further investigated in phase III trials.

[A Case of Advanced Hepatocellular Carcinoma That Caused Rapid Re-Growth Due to Lenvatinib Withdrawal].

Lenvatinib is reported to have a stronger angiogenesis-inhibiting effect in hepatocellular carcinoma(HCC)than sorafenib, but in many cases dose reduction and withdrawal are required due to the occurrence of adverse events. We report 12 cases of using lenvatinib for advanced HCC in our hospital together with a case of rapid re-growth due to withdrawal of lenvatinib. In 2 cases, metastases of HCC were controlled and radically resected. All patients required lenvatinib withdrawal due to Grade 3 adverse event, except for 2 cases that started with dose reduction. There were 3 cases in which drug withdrawal was required for 2 weeks or more, and in 2 of them, rapid re-growth of tumor was observed during the drug withdrawal and the treatment could not be continued. Although the use of lenvatinib may results in tumor shrinkage, suggesting that prolonged drug withdrawal may make disease management difficult. It is important to manage adverse events and minimize days of drug withdrawal by reducing the dose and systematically discontinuing the drug.

Our experience of repeat laparoscopic liver resection in patients with recurrent hepatocellular carcinoma.

BACKGROUND: Repeat liver resection is an effective treatment approach for patients with recurrent hepatocellular cell carcinoma (HCC). However, the surgical feasibility and oncological significance of repeat laparoscopic liver resection (r-LLR) remain unproven. This study evaluates and compares the clinical outcomes of non-anatomic r-LLR applied towards recurrent HCC, with those of primary LLR (p-LLR) for primary HCC. METHODS: This retrospective study reports 104 patients with HCC, treated with LLR between 2014 and 2018. Twenty eight of these patients underwent r-LLR for recurrent HCC. The clinical and surgical variables were reviewed for all cases. RESULTS: The analysis was limited to non-anatomic resection across both groups (r-LLR: 89% (25/28) vs. p-LLR: 80% (61/76)). There were no statistically significant differences about patient background between the two groups, with the exception of Child-Pugh classification. r-LLR surgical techniques included single-site laparoscopic adhesiolysis (32%, 8/25), Pringle maneuver (8%, 2/25), and crush-clamp method using BiClamp for hepatic parenchymal transection (72%, 18/25). No severe postoperative complications were observed in the r-LLR group. Postoperative hospital stays and procedure-related postoperative survival were similar for both groups. CONCLUSIONS: Non-anatomical r-LLR renders comparable surgical and oncological outcomes. Our data suggest that non-anatomical r-LLR is a safe and feasible therapeutic approach to recurrent HCC.

[Ascending Colon Cancer with Hemophilia A Treated with Laparoscopic Right Hemicolectomy under Control of a Blood Coagulant Factor-A Case Report].

Here, we report a case of ascending colon cancer successfully treated with laparoscopic right hemicolectomy in a 74- year-old man with a medical history of hemophilia A. He was admitted to our hospital because of bloody stool and diagnosed with type 2 ascending colon cancer based on colonoscopy findings. Preoperatively, blood transfusion and administration of recombinant factor Ⅷ products were performed. Surgery involved laparoscopic right hemicolectomy plus group 3 lymph node dissection. No complications, such as bleeding, occurred during hospitalization. The patient was discharged on postoperative day 8. There have been a few reports of laparoscopic surgery for patients with hemophilia. However, this case suggests that it can be safely performed with planned factor Ⅷ supplementation in the perioperative period.

[Proteinuria in Patients with Gastric Cancer Treated with Ramucirumab].

BACKGROUND: Ramucirumab, an antiangiogenic agent, often causes proteinuria as a characteristic adverse effect. We retro- spectively evaluated proteinuria and clarified the significance of the protein/creatinine ratio by using single urine samples from patients with advanced gastric cancer who were treated with ramucirumab. METHODS: Twenty-three patients who received ramucirumabb etween June 2015 and April 2016 were enrolled. A total of 199 urinalysis specimens were qualitatively analyzed to obtain urine protein levels and the protein/creatinine ratio, and the values were compared. RESULTS: Frequency of proteinu- ria was 43.5%(grade 1: 26.1%, grade 2: 8.7%, and grade 3: 8.7%). The protein/creatinine ratio was less than 2 in -, ±, and 1+ based on the urine protein qualitative examination; 12.5% of 2+ and 71.4% of 3+ or 4+ had a protein/creatinine ratio over 2. CONCLUSIONS: In patients with gastric cancer, treated with ramucirumab, the protein/creatinine ratio should be examined in cases of 2+, 3+ or 4+ via a qualitative examination.

Randomized, Open-Label Phase II Study Comparing Capecitabine-Cisplatin Every 3 Weeks with S-1-Cisplatin Every 5 Weeks in Chemotherapy-Naïve Patients with HER2-Negative Advanced Gastric Cancer: OGSG1105, HERBIS-4A Trial.

LESSONS LEARNED: Evidence has suggested that capecitabine-cisplatin is similar or possibly superior to S-1-cisplatin in terms of safety and efficacy for Japanese patients with advanced gastric cancer (AGC).As far as we are aware, our study is the first randomized trial of two regimens consisting of an oral fluoropyrimidine plus cisplatin in human epidermal growth receptor 2-negative AGC patients with measurable lesions. BACKGROUND: We performed a phase II study to evaluate the safety and efficacy of capecitabine plus cisplatin in comparison with S-1 plus cisplatin for first-line treatment of human epidermal growth receptor 2 (HER2)-negative advanced gastric cancer in Japan. METHODS: Eligible patients were randomly assigned to receive either capecitabine at 1,000 mg/m2 twice daily for 14 days plus cisplatin at 80 mg/m2 on day 1 every 3 weeks (n = 43) or S-1 at 40-60 mg twice daily for 21 days plus cisplatin at 60 mg/m2 on day 8 every 5 weeks (n = 41). The primary endpoint of the study was response rate. RESULTS: Response rate did not differ significantly between the capecitabine-cisplatin and S-1-cisplatin groups (53.5% vs. 51.2%, respectively, p > .999). S-1-cisplatin tended to confer a better progression-free survival (PFS; median of 5.9 vs. 4.1 months, p = .284), overall survival (OS; median of 13.5 vs. 10.0 months, p = .290), and time to treatment failure (TTF; median of 4.5 vs. 3.1 months, p = .052) compared with capecitabine-cisplatin. Common hematologic toxicities of grade 3 or 4 included anemia and neutropenia in both groups. However, anorexia, fatigue, and hyponatremia of grade 3 or 4 occurred more frequently in the capecitabine-cisplatin group. CONCLUSION: Capecitabine-cisplatin failed to demonstrate superior efficacy compared with S-1-cisplatin. The higher incidence of severe adverse events with capecitabine-cisplatin suggests that S-1-cisplatin should remain the standard first-line chemotherapy for HER2-negative advanced gastric cancer in Japan.

Clinical outcomes and prognostic factors for gastric cancer patients with bone metastasis.

BACKGROUND: Bone metastasis due to gastric cancer is rare, and the clinical features have not been fully evaluated. We investigated the clinical features, treatment outcomes, and prognostic factors in gastric cancer patients with bone metastasis. METHODS: We retrospectively collected data on 34 consecutive patients who were diagnosed radiologically with bone metastasis due to gastric cancer. We estimated the overall survival after the diagnosis of bone metastasis using the Kaplan-Meier product-limit method and evaluated which clinicopathological factors were associated with prognostic factors for survival using univariate and multivariate Cox proportional hazards regression models. RESULTS: The treatment for the primary tumor was surgery in 16 patients (47.1%) and chemotherapy in 18 patients (52.9%). The median serum alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) levels at the time of bone metastasis were 375.5 and 249 IU/L, respectively. Ten patients (29.4%) were diagnosed with bone metastasis and gastric cancer at the same time. The 6-month survival rate after the diagnosis of bone metastasis was 63.8%, and the median survival time was 227.5 days. Multivariate analysis revealed that metachronous metastasis (p = 0.035) and extraosseous metastasis (p = 0.028) were significant risk factors for poor survival. CONCLUSIONS: The prognosis of gastric cancer with bone metastasis was poor, and metachronous metastasis and extraosseous metastasis were shown to be poor prognostic factors. Serum ALP, LDH, and tumor markers are not always high, so aggressive diagnosis using appropriate modalities such as bone scan, MRI, or PET-CT may be necessary in routine practice even in asymptomatic patients.

[A Case of Recurrent Gastric Cancer with Grade 3 Proteinuria Caused by Ramucirumab plus Paclitaxel Therapy].

Proteinuria is one of the characteristic adverse events by ramucirumab(RAM)plus paclitaxel(PTX)combination therapy for advanced gastric cancer. We reported a case of recurrent gastric cancer with grade(gr)3 proteinuria caused by RAM plus PTX therapy. 77-year-old woman was underwent distal gastrectomy in 76 years old for gastric cancer that was diagnosed mucinous adenocarcinoma, fStage III C(T4aN3H0P0CY0M0)and received adjuvant chemotherapy of S-1 for 1 year. She suffered from peritoneal recurrence with ascites after 1 year and 4 months of the operation and RAM(8mg/kg; day 1 and 15)plus PTX(80mg/m2; day 1, 8 and 15)therapy was administrated as second-line chemotherapy. After 1 course, weekly PTX has been continued for gr 3 proteinuria and the ascites disappeared after 4 courses. This successful case might indicate that it was important for patients with gr 3 proteinuria as adverse event to consider discontinuance of RAM and continuation of PTX according to the proper usage guide of RAM.

[A Case of Self-Expandable Metallic Stent Placement to Treat Colon Obstruction Due to Metastatic Gastric Cancer].

A66 -year-old woman presented with abdominal pain and nausea. She was diagnosed with wall thickening of the gastric antrum and bowel obstruction caused by tumors of the splenic flexure on computed tomography. Aself -expandable metallic stent(SEMS)was placed in the splenic flexure of the colon 4 days after transanal ileus tube replacement. No complication was observed, and she could ingest a normal diet, permitting her discharge from the hospital 12 days after SEMS placement. She was diagnosed with gastric cancer(Type 4, cT4a[SE], N2, H0, P1, M1[LYM], cStage IV )on upper gastrointestinal endoscopy and computed tomography, and administration of S-1 plus oxaliplatin(SOX)was started. Nab-paclitaxel as the second-line chemotherapy was administered after 8 courses of SOX therapy because of an increase in the amount of ascites. No late complication associated with stent placement was recognized. SEMS placement was suggested to be effective for treating colon obstruction due to metastatic gastric cancer.

[Eye Disorders Associated with S-1 Chemotherapy in Gastric Cancer Patients].

Eye disorders are one of the characteristic adverse events associated with S-1 chemotherapy. In this retrospective study, we investigated the frequency and outcome of eye disorders associated with S-1 chemotherapy in gastric cancer patients. This retrospective study included 75 advanced gastric cancer patients who received S-1 monotherapy between January 2014 and December 2015. We retrospectively evaluated the frequency, Grade, and treatment of eye disorders. Eye disorders were observed in 16 patients(21%). The median time of onset was 3(range, 1-8)months. Grade 2 watering eyes, eye discharge, and conjunctivitis were reported in 14, 8, and 4 patients, respectively. Artificial tears, fluorometholone eye-drops, and both of these treatments were used in 7, 1, and 8 patients, respectively. Ophthalmologic examination was performed for 3 patients. No delay or reduction of S-1 therapy was required for the eye disorders. Eye disorders associated with S-1 therapy in gastric cancer patients did not affect treatment if managed properly using eye drops.

[Examination of Patients with Malignant Obstruction Treated with Chemotherapy after Ileo/Coleostomy].

Management for obstructive cancer of the colon diverges into many ways. The aim of this study was to evaluate the treatment course of patients with malignant obstruction after ileo/coleostomy. Thirty-six patients with malignant obstruction who underwent ileo/coleostomy in our hospital from May 2012 to January 2016were enrolled in the study. Clinical outcomes were the period before treatment initiation, chemotherapy, radiotherapy, primary lesion resection, and death, and these were retrospectively analyzed. Although 9 stomal complications occurred, no case experienced a delayed treatment start. However, patients with perioperative complications, sepsis due to the tumor, pneumonia, cerebral infractions, and ileus needed a long recovery period before treatment initiation. Patients who need ileo/coleostomy must be considered for performance status and ways to decrease perioperative complications to prevent stomal complications from chemo/radiotherapy.

[A Case of an Elderly Patient with Unresectable Gastric Cancer Treated by Paclitaxel and Ramucirumab].

An 80-year-old man was admitted to our hospital with appetite loss in December 2014. Gastroduodenal scope, abdominal computed tomography(CT), and laparoscopy revealed type 4 advanced gastric cancer(poorly differentiated adenocarcinoma) with multiple lymph node(LN)involvement and multiple peritoneal metastasis. S-1(80mg/body)was administrated between January 2015 and September 2015 in the outpatient clinic. A partial response was obtained, but a gastric tumor, ascites, and LN re-growth were observed. Since October 2015, paclitaxel(PTX)(70mg/m2; day 1, 8, and 15)and ramucir- umab(RAM)(8mg/kg; day 1 and 15)have been administered. After 2 courses, bi-weekly PTX plus RAM were continued for grade 3 neutropenia and grade 2 anorexia. The tumor and LNs partially responded, and the ascites disappeared. With this dosage and administration schedule, the partial response(PR)was maintained for approximately 8 months without any severe adverse reactions. This successful case might indicate that it is important for elderly patients with gastric cancer that progressed with prior chemotherapy regimens to consider appropriate reduction of the PTX dosage, schedule, and continuation of RAM.

[Three Cases of Bleeding from Advanced Gastric Cancer during Chemotherapy Treated with Transcatheter Arterial Embolization(TAE)].

Case 1: An 71-year-old man underwent chemotherapy with S-1 plus trastuzumab to treat type 3 gastric cancer that was diagnosed as Stage IV tubular adenocarcinoma(T4b[Panc], N3, H0, CY1, P0, M1). For anemia and active bleeding from the tumor, transcatheter arterial embolization(TAE)was performed with metallic coils on the splenic artery. Infarction of the spleen and left pleural effusion were observed. Second-line paclitaxel(PTX)chemotherapy was administered 4 weeks after TAE. Case 2: An 76-year-old man underwent chemotherapy with S-1 plus cisplatin to treat type 3 gastric cancer that was diagnosed as Stage IV tubular adenocarcinoma(T4a, N3, H0, P1, M1). For anemia and active bleeding from the tumor, TAE with gelatin sponge(Serescure®)was performed on the left and right gastric artery. Radiotherapy(31 Gy)with S-1 was performed because TAE was not effective for bleeding. After chemoradiotherapy, nab-PTX was administered. Case 3: An 74- year-old man underwent second-line chemotherapy with nab-PTX to treat type 4 advanced gastric cancer that was diagnosed as Stage IV tubular adenocarcinoma(T4a, N3, H1, P0, M1). For progression of anemia due to tumor bleeding, TAE with gelatin sponge(Serescure®)was performed on the left gastric artery. TAE was effective, and he was discharged from the hospital. In 2 of 3 cases, hemostasis was achieved by TAE. Therefore, TAE is effective to decrease bleeding from gastric cancer during chemotherapy.

[Clinical Experience of Ramucirumab for Treating Advanced Gastric Cancer].

BACKGROUND: The REGARD and RAINBOW trials showed that ramucirumab(RAM)alone and RAM plus paclitaxel(PTX) were effective therapies for advanced gastric cancer patients previously treated with chemotherapy. In this retrospective study, we evaluated the safety and efficacy of RAM alone and PTX plus RAM in such patients. METHODS: Patients who were received RAM at 8mg/kg or RAM plus PTX at 80mg/m2(on days 1, 8, and 15 of a 28-day cycle)between June 2015 and March 2016 were enrolled in this study. We compared the clinical outcome of RAM alone(RAM group, n=10)with that of RAM plus PTX(PTX+RAM group, n=13). RESULTS: The RAM group contained many more patients with poor performance status or prior chemotherapy of 2 or more regimens than the PTX+RAM group. All patients in both groups received chemotherapy on an outpatient basis. One case of grade 3 or 4 hematological adverse events was found in the RAM group and 6 cases were found in the PTX+RAM group. The overall response rate was 10% in the RAM group and 30% in the PTX+RAM group. Progression-free survival was 54 days in the RAM group and 187 days in the PTX+RAM group(p=0.0374). Overall survival was 158 days in the RAM group and was not reached in the PTX+RAM group(p=0.1091). CONCLUSIONS: RAM alone and RAM plus PTX can be administered safely on an outpatient basis and are beneficial for advanced gastric cancer patients previously treated with chemotherapy.

[Investigation of the Safety of and Patient Satisfaction with iEat®, the Support Food for the Recovery of Eating Function in Patients with Carcinomatosis - Related Gastrointestinal Passage Disorder].

OBJECTIVE: iEat®, a support food for the recovery of eating function, is food that can be easily masticated with little power and has suitable fluidity for enzyme processing, regardless of its normal appearance. We provided iEat® to 5 patients with carcinomatosis-related gastrointestinal passage disorder who could take fluid foods and investigated the stability of iEat® and patient satisfaction with the food. METHODS: We provided regular diets for lunch on the first and 7th day, and provided iEat® from the 2nd to the 6th day. The stability of iEat(R) was evaluated based on the presence and grade of abdominal pain, diarrhea, sense of abdominal distension, nausea, and vomiting, according to the Common Terminology Criteria for Adverse Events (CTCAE v4.0, JCOG). The patients assessed their satisfaction by using 6 grades of taste, appearance, amount, difficulty of intake, and overall valuation. RESULTS: One patient could not continue the study because of vomiting from overeating of iEat(R). In the other patients, iEat(R) induced approximately the same adverse events as did the regular diets. All of the patients expressed better satisfaction with iEat® than with the regular diets. CONCLUSION: Although patient management for overeating is necessary, iEat® might provide good quality of life in terms of eating satisfaction to the patients with carcinomatosis-related gastrointestinal passage disorder.

[Intraluminal Type Gastrointestinal Stromal Tumor Resected by Single-Incision Percutaneous Endoscopic Intragastric Surgery--A Case Report].

We report a patient with gastric gastrointestinal stromal tumor (GIST) who underwent single-incision percutaneous endoscopic intragastric surgery. The patient was a 70-year-old man. Esophagogastroduodenoscopy and abdominal computed tomography revealed the presence of an intraluminal type gastric submucosal tumor, 4 cm in diameter, in the posterior wall of the gastric body. Laparoscopic partial gastrectomy was performed via a single incision made in the epigastric region. The postoperative course was uneventful. The pathological diagnosis was a low-risk GIST. This method is easy and safe to perform; therefore, we consider it to be an important option for the treatment of intraluminal type gastric GIST.

[A Case of Bone Metastasis from Early Gastric Cancer after a Five-Year Disease-Free Interval Following Gastrectomy].

A woman in her 50s underwent distal gastrectomy and D1+b dissection in December 2005 for early gastric cancer that was diagnosed as a signet-ring-cell carcinoma, fStage Ⅱ (T1a, N2, H0, P0, CY0, M0) with 12 lymph node metastases in the second field. Multiple bone metastases were diagnosed on the basis of CT and bone scintigraphy findings and serum ALP elevation (2,743 IU/L) I n December 2010. Fourteen courses of S-1 plus CDDP and 4 mg of zoledronate were administered from January to September in 2011. Pancytopenia, D-dimmer elevation, myelocytes, and metamyelocytes were observed in October 2012, indicating she had bone marrow metastasis. She was treated with a transfusion, anti-DIC therapy, and paclitaxel. She died from gastric cancer in December 2012. We report a rare case of recurrence with bone metastasis from early gastric cancer. S-1 plus CDDP chemotherapy and zoledronate therapy is an effective treatments for multiple bone metastases from gastric cancer.

[A Case of Rectal Stenosis For Gastric Cancer Recurrence Effectively Treated with a Colonic Stent].

A man in his 70s underwent distal gastrectomy and D1 dissection with Roux-en-Y reconstruction in March 2009 for advanced gastric cancer with peritoneal metastasis. He was diagnosed with signet-ring cell carcinoma, Stage Ⅳ(T4a, N3a, H0, P1, CY1, M1) and R2. Seventeen cycles of S-1 plus CDDP were administered from April 2009 to December 2010 and 19 cycles of S-1 monotherapy were administered from January 2011 to March 2014. He developed peritoneal recurrence with serum tumor marker elevation in May 2014. Stenosis of the common bile duct, hydronephrosis, and rectal stenosis in Ra-Rs was observed in June 2014. A bile duct stent and a double J catheter was inserted. A colonic stent (NitiTM, 22 mm×6 cm) was also inserted. He could eat after the surgery and was discharged from the hospital. We suggest that a colonic stent is an effective treatment for colon stenosis due to peritoneal metastasis from gastric cancer.