Hand-assisted laparoscopic splenectomy and gastropancreatic fold division: a less-invasive simplified technique of Hassab's procedure for refractory esophagogastric varices.

Some patients with refractory esophagogastric varices require surgery, such as gastric devascularization and splenectomy (Hassab's procedure). However, these patients are at risk of perioperative morbidities when undergoing devascularization to develop collateral vessels. We performed a more simplified procedure, splenectomy, and en bloc gastropancreatic fold division (GPFD) with hand-assisted laparoscopic surgery. Four patients with refractory esophagogastric varices and portal hypertension underwent splenectomy and GPFD. We reviewed patients' perioperative laboratory and morphological data, operative variables, and postoperative outcomes. Esophagogastric varices improved in 3 (75%) of the 4 patients. In one patient, esophageal varices (F1RC0) were observed 3 years after surgery, but they required no treatment and only received follow-up. Treatment with splenectomy and GPFD is not only less invasive than Hassab's procedure but also provides effective outcomes for refractory esophagogastric varices.

Efficacy of neoadjuvant chemotherapy in patients with high-risk resectable colorectal liver metastases.

BACKGROUND: The role of preoperative neoadjuvant chemotherapy (NAC) in patients with resectable colorectal liver metastases (CRLM) remains undetermined. This study aimed to assess the efficacy of NAC in patients with resectable CRLM, especially in high-risk subgroups for recurrence, with special reference to synchronicity and the CRLM grade in the Japanese classification system. METHODS: A retrospective analysis of a multi-institutional cohort who was diagnosed with resectable CRLM was performed. CRLM was classified into three grades (A, B, and C) according to the combination of H stage (H1: ≤ 4 lesions and ≤ 5 cm, H2: ≥ 5 lesions or > 5 cm, H3: ≥ 5 lesions and > 5 cm), nodal status of the primary tumor (pN0/1: ≤ 3 metastases, pN2: ≥ 4 metastases), and the presence of resectable extrahepatic metastases. RESULTS: Among 222 patients with resectable CRLM, 97 (43.7%) had synchronous CRLM. The surgical failure-free survival (SF-FS) of patients with synchronous CRLM (without NAC) was significantly worse than that of patients with metachronous CRLM (P = 0.0264). The SF-FS of patients with Grade B/C was also significantly worse than that of Grade A (P = 0.0058). Among the 53 patients with synchronous and Grade B/C CRLM, 31 were assigned to NAC, and all of them underwent liver surgery. In this high-risk subgroup, the SF-FS and OS in the NAC group were significantly better than those in the upfront surgery group (P < 0.0001 and P = 0.0004, respectively). CONCLUSIONS: Patients with synchronous and Grade B/C CRLM could be good candidates for indication of NAC.

Thrombotic Microangiopathy Following Chemotherapy with S-1 and Cisplatin in a Patient with Gastric Cancer: A Case Report.

BACKGROUND: Thrombotic microangiopathy (TMA) represents a spectrum of serious disorders characterized by occlusive microvascular thrombosis, thrombocytopenia and end-organ damage. TMA is associated with a broad range of conditions and is also a well-described complication of both cancer and its treatment. CASE REPORT: A 77-year-old Japanese woman underwent S-1 and cisplatin chemotherapy for treatment of advanced gastric cancer with multiple lymph node and liver metastases. She was found with severe anemia and thrombocytopenia during the third course of chemotherapy. She was diagnosed with TMA based on thrombocytopenia, schistocytosis, hemolytic anemia and renal dysfunction. She underwent treatment with plasmapheresis; however, her response to treatment was poor and died on day 16 of hospitalization. The autopsy performed revealed microthrombi in the glomeruli and tubulonecrosis in the kidneys. CONCLUSION: This is the first case report of TMA in association with the use of S-1 and cisplatin. Therapists have to take account of TMA when using S-1 and cisplatin treatment.

Expression of the anaphylatoxin C5a receptor in gastric cancer: implications for vascular invasion and patient outcomes.

The C5a receptor (C5aR) expressed in various types of cancers is involved in C5a-induced cancer cell invasion. However, its role in gastric cancer has not yet been fully elucidated. Therefore, we studied the clinical significance of C5aR expression in gastric cancer. The association of C5aR expression in gastric cancer, determined by immunostaining using the anti-C5aR antibody, with clinicopathological parameters and outcomes was evaluated in 148 patients. Further, the association of C5aR expression in liver metastatic sites with clinicopathological parameters was investigated in a separate cohort of 58 patients who underwent hepatectomy. High tumoral C5aR expression (n = 45, 30.4 %) was significantly related to tumor location, cancer invasion depth, vascular and lymphatic invasion, and tumor stage. The 5-year recurrence-free and overall survival rates of patients with high tumoral C5aR expression were significantly lower than those of patients with low tumoral C5aR expression (50.9 vs. 84.2 %, P = 0.002 and 58.8 vs. 86.1 %, P = 0.007, respectively). The incidence of liver metastasis was significantly higher in patients with high tumoral C5aR expression (13.3 %) than in those with low tumoral C5aR expression (3.9 %; P = 0.04). C5aR expression at liver metastatic sites was associated with the C5aR expression status at the primary site (P = 0.0004), vascular invasion at the primary site (P = 0.04), and tumor size at the metastatic site (P = 0.01). C5aR expression in gastric cancer was associated with cancer progression, liver metastasis, and poor prognosis. Therefore, C5aR may represent a prognostic factor and therapeutic target in gastric cancer.

Surgical treatment of liver metastasis of gastric cancer: a retrospective multicenter cohort study (KSCC1302).

BACKGROUND: The necessity of surgical treatment of liver metastases of gastric cancer is still controversial. PATIENTS AND METHODS: We conducted a multicenter retrospective cohort study of liver-limited metastasis of gastric cancer treated surgically between 2000 and 2010. In this study, 103 patients were registered, with nine patients excluded from the analysis as they did not meet the eligibility criteria. RESULTS: Of the 94 patients, 69 underwent surgical resection, 11 underwent surgical resection combined with radiofrequency ablation or microwave coagulation therapy for small or deep tumors, and 14 underwent radiofrequency ablation or microwave coagulation therapy only. Synchronous and metachronous metastases were found in 37 and 57 patients, respectively. The 3- and 5-year overall survival rates of all the patients were 51.4 and 42.3 %, respectively. The 3- and 5-year relapse-free survival rates were 29.2 and 27.7 %, respectively. No significant difference in prognosis was observed between the patients who underwent surgical resection and those who underwent ablation therapy. The patients with hepatic solitary lesions and low-grade lymph node metastases of primary gastric cancer had significantly better overall survival and relapse-free survival. CONCLUSIONS: To our knowledge, this study is the largest series and first multicenter cohort study of liver-limited metastasis of gastric cancer. The study indicated that patients with a single liver metastasis with a grade lower than N2 lymph node metastasis of the primary lesion are the best candidates for liver resection.

Phase II trial of an alternating regimen consisting of first-line mFOLFOX6 plus bevacizumab and FOLFIRI plus bevacizumab for patients with metastatic colorectal cancer: FIREFOX plus bevacizumab trial (KSCC0801).

OBJECTIVES: The purpose of this phase II study was to explore the efficacy and safety of an alternating regimen consisting of folinic acid, 5-fluorouracil (5-FU) and oxaliplatin (mFOLFOX6) plus bevacizumab, and folinic acid, 5-FU and irinotecan (FOLFIRI) plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer. METHODS: Fifty-two patients with metastatic colorectal cancer received an alternating regimen consisting of four cycles of mFOLFOX6 plus bevacizumab followed by four cycles of FOLFIRI plus bevacizumab until disease progression. The primary endpoint was progression-free survival. RESULTS: The median age was 60 years (range 37-75 years). Median progression-free survival was 14.2 months (95 % confidence interval [CI] 10.6-16.3) and median overall survival was 28.4 months (95 % CI 22.6-39.1). The overall response rate was 60.0 % (95 % CI 45.2-73.6). Regarding toxicity, the commonest grade 3-4 hematological adverse events were neutropenia (34.6 %) and leukopenia (7.7 %), and the commonest grade 3-4 non-hematological adverse events were anorexia (13.5 %), fatigue (9.6 %), nausea (9.6 %), and vomiting (9.6 %). Bevacizumab-related grade 3-4 adverse events included hypertension (1.9 %) and thrombosis (1.9 %). CONCLUSIONS: An alternating regimen consisting of mFOLFOX6 plus bevacizumab and FOLFIRI plus bevacizumab is an effective and well-tolerated first-line chemotherapy combination for patients with metastatic colorectal cancer.

Phase II Trial of S-1 and Oxaliplatin Plus Cetuximab for Colorectal Cancer Patients with Initially Unresectable or Not Optimally Resectable Liver Metastases (KSCC1002).

BACKGROUND: The Kyushu Study Group of Clinical Cancer (KSCC) conducted phase II trials of KSCC1002 (UMIN000001308) concerning liver resectability after first-line treatment of initially unresectable or not optimally resectable colorectal liver metastases in a prospective, multicenter study. METHODS: Patients with wild-type KRAS received 4-6 cycles of S-1 and oxaliplatin (SOX) plus cetuximab. Liver resectability was evaluated subsequently with the liver resection rate as the primary endpoint. RESULTS: Of the 33 patients enrolled between March 2010 and July 2013, the median number of administration cycles was 4 (range 0-10). The overall response rate was 63.6 % (95 % confidence interval [CI] 45.1-79.6 %). Liver resection was possible in 16 of 33 (48.5 %) patients, and there were 13 R0 cases (39.4 %). We conducted a central review of liver resectability evaluated by five liver surgeons, and the resectability increased from 18.2 to 66.7 % after chemotherapy, based on imaging. The median overall survival for all 33 cases was 31.6 months (95 % CI 14.8-not reached). The median progression-free survival was 9.7 months (95 % CI 6.2-11.8). CONCLUSIONS: SOX plus cetuximab is safe and effective for advanced colorectal cancer with limited liver metastasis, and may lead to high liver resectability.

Repeat hepatectomies for hepatic malignant lymphoma and hepatocellular carcinoma associated with chronic hepatitis C: report of a case.

We report a case of repeat hepatectomies for hepatic malignant lymphoma and hepatocellular carcinoma (HCC). A 75-year-old man with chronic hepatitis C underwent partial hepatectomy for a 25 mm hepatic tumor in S5. The histological diagnosis was diffuse large B-cell malignant lymphoma and as postoperative (18)F-fluorodeoxyglucose-positron emission tomography showed no hot spots, the mass was presumed to be primary hepatic lymphoma. Thus, adjuvant systemic chemotherapy was given following the hepatectomy. Abdominal ultrasonography, done 12 months after the hepatectomy, showed a hepatic tumor in S6 and repeat partial hepatectomy was performed. This tumor was histologically diagnosed as HCC.

Localized biphasic type malignant mesothelioma arising in the peritoneum: Report of a case.

This report describes a rare case of localized malignant biphasic (mixed epithelioid and sarcomatoid) mesothelioma arising in the peritoneum. A 69-year-old male with a history of asbestos exposure, complaining of a painful mass in the left chest wall, was found via computed tomography (CT) to have a tumor in the left peritoneum. The resected tumor was histologically and immunohistochemically consistent with a malignant mesothelioma with mixed epithelioid and sarcomatoid type and no distant metastasis. The diagnosis of localized malignant biphasic mesothelioma arising in the peritoneum was appropriate because there was no evidence of any other primary tumor.

Significance of hepatic resection for hepatocellular carcinoma with sustained virological response to interferon therapy for chronic hepatitis C.

AIM: A sustained virological response (SVR) to interferon (IFN) therapy for chronic hepatitis C decreases but does not eliminate the risk of hepatocellular carcinoma (HCC). The significance of hepatectomy for HCC in patients with SVR has not been clarified. The short- and long-term outcomes of hepatectomy for HCC in patients with SVR were studied. METHODS: From 2006-2011, 69 patients with chronic hepatitis C underwent hepatic resection for primary HCC in our hospital. Of these, 12 patients (17.4%) had SVR to IFN therapy at the time of hepatectomy. The clinicopathological factors and long-term outcomes of these patients were retrospectively reviewed and were compared with those of patients without SVR. RESULTS: The mean time from achievement of SVR to diagnosis of HCC was 62 months (range, 7-174). The histological inflammation of liver parenchyma had improved after IFN therapy in SVR cases. The preoperative serum alanine transaminase, albumin and prothrombin time were significantly preserved in patients with SVR. Intraoperative blood loss and blood transfusion rate were lower, and recurrence-free survival rate was significantly higher, in patients with SVR. CONCLUSION: In patients undergoing hepatectomy for HCC, those with SVR had better perioperative safety and a more favorable long-term prognosis than those without SVR.

Large simple hepatic cysts leading to gastric fundal varices in a noncirrhotic patient.

A 74-year-old noncirrhotic woman presented with abdominal distension and pain in the right hypochondrium. Contrast-enhanced computed tomography (CT) demonstrated multiple large simple liver cysts occupying the right lobe of the liver, the largest of which was 19 cm in diameter. Gastric varices were enhanced in the fundus of the stomach. The patient underwent surgery to deroof the hepatic cysts with ablation using argon beam coagulation. Esophagogastroduodenoscopy (EGD) showed that the portal hypertensive gastropathy was ameliorated after the operation; however, the fundal varices were only slightly decreased. After the operation, we observed that the hepatic vein waveform gradually changed from a gently curved pattern to a normal triphasic pattern. We treated the fundal varices with balloon-occluded retrograde transvenous obliteration 3 months after the initial operation. We describe our successful treatment of this rare case and discuss the utility of hepatic vein waveform analysis in the study of portal hypertension.

Risk factors of bile leakage after hepatectomy for hepatocellular carcinoma.

BACKGROUND/AIMS: To identify the risk factors for postoperative biliary complications after hepatic resection for hepatocellular carcinoma. METHODOLOGY: The subjects were 123 patients who underwent hepatic resection for hepatocellular carcinoma between January 2006 and December 2010. Perioperative factors related to postoperative bile leakage were studied. RESULTS: Postoperative bile leakage occurred in eight (6.5%) of the patients. Univariate analysis showed that liver fibrosis or cirrhosis (p=0.007), long operation time (>5 hours) (p=0.002), major hepatic resection (p=0.024) and hepatectomy including Couinaud's segment 4 (p=0.0078) or segment 5 (p=0.023) were associated with an incidence of bile leakage. From multivariate analysis, operation time (relative risk=6.10, p=0.026) or resection of segment 4 (relative risk=6.86, p=0.017) were found to be independent risk factors for bile leakage. CONCLUSIONS: Prolonged operation time and hepatectomy including segment 4 led to a high risk for postoperative bile leakage in this series of patients.

Assessment of delayed gastric emptying after major hepatectomy using a 13C-acetic acid breath test.

PURPOSES: Delayed gastric emptying (DGE) after hepatectomy affects the quality of life of patients, although the causes and related conditions have not been investigated. This study evaluated the relationship between hepatectomy and DGE by the objective assessment of gastric emptying (GE). METHODS: Nineteen patients who underwent major hepatectomy were prospectively enrolled in the study. Their GE was studied using the (13)C-acetic acid breath test before and after hepatectomy. The results of the GE analysis were correlated with the postoperative course after hepatectomy. RESULTS: Clinically evident DGE, which was defined as the inability to take in an appropriate amount of solid food orally by postoperative day 14, was not found in these patients, but the gastric half-emptying times before and after hepatectomy were 20.2 ± 9.7 and 28.6 ± 12.2 min, respectively (P = 0.01). The GE time was significantly delayed in patients aged ≥ 41 years, or who underwent right hemihepatectomy. CONCLUSIONS: Gastric emptying was significantly inhibited in patients who underwent major hepatectomy, and aging and a right-sided hemihepatectomy may be related to the development of DGE.

Incidence and predictors of deep venous thrombosis after abdominal oncologic surgery: prospective Doppler ultrasound screening.

BACKGROUND: Venous thromboembolism is a relatively rare but serious complication of abdominal surgery. This study evaluated the incidence and risk factors for the development of deep venous thrombosis (DVT) after abdominal oncologic surgery using color Doppler ultrasonography (DUS). METHODS: This study enrolled 132 consecutive patients who underwent elective abdominal surgery for malignant tumors. Patients were investigated for DVT using DUS on postoperative day 7 ± 2. Correlations between the incidence of DVT and clinicopathologic parameters and the postoperative course were evaluated. RESULTS: DVT was found in 15 patients (11.4%) using DUS. Clinically evident venous thromboembolism, including pulmonary embolism, was not found in these patients. The incidence of DVT was significantly higher in females (P=0.002), patients with a lower body mass index (P=0.008), and patients with a higher preoperative D-dimer level (P<0.0001). CONCLUSIONS: DUS is noninvasive and is useful for postoperative DVT screening. Thromboprophylaxis is essential in high-risk patients who have undergone abdominal oncologic surgery.

An unusual enteropathy-associated T-cell lymphoma with MYC translocation arising in a Japanese patient: a case report.

Enteropathy-associated T-cell lymphoma (EATL) is a rare peripheral T-cell lymphoma classified into 2 types, with or without celiac disease, based on histology. Type 2 EATL is less commonly associated with celiac disease, in which cells are characterized by being monomorphic and small- to medium-sized. Cells are characterized by CD8 and CD56 expression and c-MYC oncogene locus gain. We present an atypical case of type 2 EATL in the jejunum, with human T-lymphotropic virus-1 that was CD4- CD8+ CD56- CD30- CD25- TIA-1+ and granzyme B+ on immunohistological staining. It also displayed translocation of chromosome 8p24 (c-MYC), as determined by fluorescent in situ hybridization. Mucosal spreading and intraepithelial invasion by lymphoma with villous atrophy were detected adjacent to the mucosal layer. The lymphoma may be derived from intraepithelial CD8+ T cells, similar to celiac disease.

Severe sepsis caused by Aeromonas hydrophila in a patient using tocilizumab: a case report.

INTRODUCTION: Aeromonas species do not commonly cause disease in humans. However, when disease is seen, it often occurs in patients with underlying immunosuppression or malignancy and has a high fatality rate. CASE PRESENTATION: A 72-year-old Japanese woman with rheumatoid arthritis treated with tocilizumab (which has an immunosuppressive effect) presented with severe epigastric pain. She had a fever with chills, hypotension and jaundice. She was diagnosed with acute suppurative cholangitis and treated with cefoperazone-sulbactam and an endoscopic drainage was performed. Jaundice was slightly improved, but the shock state and inflammatory reactions were prolonged as typical of septic shock. On the second day after admission, an electrocardiogram showed ST segment elevation and echocardiography showed ventricular wall dysfunction. Coronary arteries were patent in coronary angiography and she was diagnosed with stress-induced cardiomyopathy. Blood cultures showed Aeromonas hydrophila. A stool culture was negative for A. hydrophila. On day six, her white blood cell count and neutrophils were normalized and cefoperazone-sulbactam treatment was halted. Left ventricular function normalized on day twelve and a laparoscopic cholecystectomy for cholelithiasis was performed on the 16th day of hospitalization. A culture from the bile showed A. hydrophila. Eighteen days after surgery, tocilizumab treatment was restarted and there were no complications. Two months after restarting tocilizumab, our patient is stable without any serious events. CONCLUSION: We present a rare case of A. hydrophila sepsis and acute suppurative cholangitis in an elderly patient with gallstones and rheumatoid arthritis using tocilizumab. This clinical course may suggest that preemptive treatment for cholelithiasis prior to using molecular-targeting agents might be feasible in elderly patients.

A multicenter phase II clinical study of oxaliplatin, folinic acid, and 5-fluorouracil combination chemotherapy as first-line treatment for advanced colorectal cancer: a Japanese experience.

PURPOSE: This multicenter phase II study was designed to determine the efficacy and tolerability of oxaliplatin in combination with levofolinate and infusion 5-fluorouracil (FOLFOX4) as first-line therapy for Japanese patients with unresectable metastatic colorectal cancer. METHODS: Sixty consecutive patients with histologically confirmed advanced or metastatic colorectal cancer were enrolled in the study. Treatment was repeated every 2 weeks until disease progression or unacceptable toxicity occurred. RESULTS: Two patients were ineligible. Toxicity was evaluated in 60 patients, who had received a part or all of the protocol therapy. A partial response was observed in 20 patients. The overall response rate was 34.5% (95% CI, 22.5%-48.1%) and the tumor control rate (partial response + stable disease) was 82.8%. The median progression-free survival was 6.9 months (95% CI, 5.1-9.8 months), and the median overall survival was 31.5 months (95% CI, 18.1-40.1 months). There were no toxicity-related deaths. Grade 3 or 4 neutropenia occurred in 48.3% of patients and often caused a delay in the subsequent treatment course. Mild to moderate cumulative peripheral sensory neuropathy affected 71.7% of patients. CONCLUSION: The results showed good tolerability and efficacy for first-line FOLFOX4 in the treatment of patients with advanced colorectal cancer, indicating the promise of this regimen as first-line therapy for advanced colorectal cancer in the Japanese population.

Physical assessment immediately after lobectomy via miniposterolateral thoracotomy assisted by videothoracoscopy for non-small cell lung cancer.

PURPOSE: We evaluated the invasiveness of videothoracoscopy-assisted mini-posterolateral thoracotomy (VAmPLT) for non-small cell lung cancer (NSCLC). METHODS: This study prospectively analyzed 50 NSCLC patients who underwent VAmPLT lobectomy. We measured maximal negative inspiratory pressure (PImax), maximal positive expiratory pressure (PEmax), quadriceps strength (QS), 6-min walk test (6mWT), and postoperative pain during the perioperative period. We then compared the results of the 6mWT and the postoperative pain of the VAmPLT lobectomy patients with those of a control group of 50 NSCLC patients who underwent standard posterolateral thoracotomy (PLT) techniques just prior to implementation of the VAmPLT lobectomy. RESULTS: The PImax and PEmax at the baseline, then on postoperative days (PODs) 1, 7, and 14 were 125% ± 5% and 120% ± 4%, 69% ± 4% and 62% ± 4%, 115% ± 5% and 100% ± 4%, and 123% ± 4%, and 110% ± 4%, respectively. The QS at the baseline, then on PODs 7 and 14 was 138% ± 5%, 129% ± 6%, and 133% ± 5%, respectively. Improvement from the baseline was seen in PImax by POD 7, and in PEmax and QS by POD 14. The 6mWT results and the level of postoperative pain after VAmPLT lobectomy were superior to those after PLT. CONCLUSIONS: The advantages of VAmPLT lobectomy over PLT include less postoperative pain and earlier recovery of physical function.

Preoperative diagnostic value of single-balloon enteroscopy for successful surgical treatment of three independent-origin gastrointestinal malignant tumors: report of a case.

A 67-year-old woman with bloody stools underwent esophagogastroduodenoscopy and colonoscopy, which revealed the presence of a submucosal tumor in the stomach and an adenocarcinoma in the ascending colon. Preoperative screening disclosed an additional 10-cm tumor in the abdomen between the gastric and colonic lesions. Single-balloon enteroscopy was therefore performed. A nonstenotic, circumferential, bleeding ulcerative lesion was found in the jejunum, and the biopsy revealed malignant lymphoma (ML). A partial resection of the small intestine, ascending colectomy, and wedge resection of the stomach were performed, then systemic chemotherapy for ML was started 2 weeks after surgery. Triple gastrointestinal malignant tumors with different histologies are extremely rare, and have not been previously reported. Single-balloon enteroscopy in this case led to a definite diagnosis by biopsy, thus allowing the patient to receive chemotherapy as soon as possible after surgery.