Role of α-gal epitope/anti-Gal antibody reaction in immunotherapy and its clinical application in pancreatic cancer.

Pancreatic cancer is one of the most common causes of death from cancer. Despite the availability of various treatment modalities, such as surgery, chemotherapy and radiotherapy, the 5-year survival remains poor. Although gemcitabine-based chemotherapy is typically offered as the standard care, most patients do not survive longer than 6 months. Therefore, new therapeutic approaches are needed. The α-gal epitope (Galα1-3Galß1-4GlcNAc-R) is abundantly synthesized from glycoproteins and glycolipids in non-primate mammals and New World monkeys, but is absent in humans, apes and Old World monkeys. Instead, they produce anti-Gal antibody (Ab) (forming approximately 1% of circulating immunoglobulins), which specifically interacts with α-gal epitopes. Anti-Gal Ab can be exploited in cancer immunotherapy as vaccines that target antigen-presenting cells (APC) to increase their immunogenicity. Tumor cells or tumor cell membranes from pancreatic cancer are processed to express α-gal epitopes. Subsequent vaccination with such processed cell membranes results in in vivo opsonization by anti-Gal IgG in cancer patients. The interaction of the Fc portion of the vaccine-bound anti-Gal with Fcγ receptors of APC induces effective uptake of the vaccinating tumor cell membranes by the APC, followed by effective transport of the vaccinating tumor membranes to the regional lymph nodes, and processing and presentation of the tumor-associated antigens. Activation of tumor-specific B and T cells could elicit an immune response that in some patients is potent enough to eradicate the residual cancer cells that remain after completion of standard therapy. This review addresses these topics and new avenues of clinical importance related to this unique antigen/antibody system (α-gal epitope/anti-Gal Ab) and advances in immunotherapy in pancreatic cancer.

Prognosis of gastric carcinoma patients aged 85 years or older who underwent surgery or who received best supportive care only.

BACKGROUND: There is controversy regarding strategies for treating very elderly patients with gastric carcinoma. We aimed to assess survival after surgery in very elderly patients according to their clinical characteristics. METHODS: Gastric cancer patients aged ≥85 years were retrospectively reviewed. There were no significant differences in clinical characteristics between 58 patients with curative resection (OP group) and 32 patients with best supportive care alone (BSC group) in cancer stage IA-IIIC and with a performance status of 0-3. RESULTS: Overall survival (OS) was significantly better in the OP group than in the BSC group in females [hazard ratio (HR) 0.27, 95 % confidence interval (CI) 0.12-0.57, P < 0.001] but not in males (HR 0.71, 95 % CI 0.35-1.49, P = 0.35). OS was significantly better in the OP group in patients aged 85-89 years (HR 0.44, 95 % CI 0.25-0.78, P = 0.006) but not in patients aged ≥90 years (HR 0.47, 95 % CI 0.12-1.66, P = 0.24). OS was significantly better in the OP group in patients with stage IB-IIIC cancer (HR 0.29, 95 % CI 0.14-0.58, P < 0.001) but not in patients with stage IA cancer (HR 0.52, 95 % CI 0.21-1.27, P = 0.15). CONCLUSIONS: Females, patients aged 85-89 years, and patients with stage IB-IIIC cancer had significantly better OS with surgery than without. For males, patients aged ≥90 years, or stage IA patients, the decision to perform surgery should be carefully made, and BSC might be an optimal strategy.

Quality of gastric cancer care in designated cancer care hospitals in Japan.

OBJECTIVE: To develop a set of process-of-care quality indicators (QIs) that would cover a wide range of gastric cancer care modalities and to examine the current state of the quality of care provided by designated cancer care hospitals in Japan. DESIGN: A retrospective medical record review. SETTING: Eighteen designated cancer care hospitals throughout Japan. PARTICIPANTS: A total of 1685 patients diagnosed with gastric cancer in 2007. MAIN OUTCOME MEASURES: Provision of care to eligible patients as described in the 29 QIs, which were developed using an adaptation of the RAND/UCLA (University of California, Los Angeles) appropriateness method by a panel of nationally recognized experts in Japan. RESULTS: Overall, the patients received 68.3% of the care processes recommended by the QIs. While 'deep venous thrombosis prophylaxis before major surgery' was performed for 99% of the cases, 'documentation before endoscopic resection' was completed for only 12% of the cases. The chemotherapy care was less likely to meet the QI standards (61%) than pre-therapeutic care (76%), surgical treatment (66%) and endoscopic resection (71%; overall difference: P < 0.001). A comparison based on the types of care showed that documentation and patient explanation were performed less frequently (60 and 53%, respectively) than were diagnostic and therapeutic processes as recommended in the QIs (85%; overall P < 0.001). CONCLUSIONS: Although many required care processes were provided, some areas with room for improvement were revealed, especially with respect to chemotherapy, documentation and patient explanation. Continuous efforts to improve the quality and develop a system to monitor this progress would be beneficial in Japan.

[Long-term survival of a case of advanced cancer of the esophagogastric junction with complete response to low-dose 5-fluorouracil and cisplatin chemotherapy].

A 58-year-old man was admitted to the author's institution with complaints of dysphagia and tarry stool. An advanced squamous cell carcinoma of the esophagogastric junction was revealed by endoscopy. The clinical stage was GE, T4, N1, H0, M0, cStageIVa, according to the Japanese Classification of Esophageal Cancer. Low-dose FP chemotherapy(continuous 5-FU div of 500mg/day with intermittent CDDP div of 10mg/day)was used. The tumor size was remarkably reduced while the side effects were trivial. A clinically complete response was recognized with CT and with pathological findings from endoscopic biopsy. As a recurrence was diagnosed in the off-treatment period, the same regimen was resumed. Soon, a complete response was again. The patient is doing well with no reoccurrence after almost 10 years, with a low-dose FP chemotherapy.

Treatment for gastric carcinoma in the oldest old patients.

BACKGROUND: The strategy for treating extremely aged patients with gastric carcinoma is controversial. This study reviews the prognoses of patients aged 85 years and older who were diagnosed with gastric carcinoma. METHODS: One hundred seventeen patients aged 85 years and older were diagnosed as having gastric carcinoma after 1969 in our institution. After excluding those at stage IV, 36 cases underwent curative resection and 30 cases received best supportive care (BSC), which we reviewed retrospectively. RESULTS: Surgical methods included distal gastrectomy for 28 cases, total gastrectomy for five cases, and other procedures for three cases. Postoperatively, pneumonia developed in four cases, anastomotic leakage in two cases, and pancreatic fistula in one case. Two patients died of pneumonia within 1 month of surgery. Univariate analysis demonstrated that age, surgery, performance status, and sodium level were statistically significant prognostic factors. Multivariate analysis demonstrated that surgery was the only independent prognostic factor. When patients with a performance status of 4 were excluded, the clinical characteristics of the surgery group (n = 36) and BSC group (n = 20) were statistically identical, and the overall survival was significantly better in the surgery group (p = 0.0078). CONCLUSIONS: Postoperative outcomes were relatively acceptable. Surgery may be feasible and beneficial even for extremely aged patients 85 years and older, except for those with a performance status of 4.

Laparoscopic resection of intra-abdominal esophageal duplication cyst.

Esophageal duplication cysts are frequently encountered in the mediastinum and rarely in the abdomen. A case of laparoscopic resection of an intra-abdominal esophageal duplication cyst is reported. An incidental 4.5 x 4.0 x 3.5-cm, well-circumscribed, homogenous mass anterior to the intra-abdominal esophagus was detected on staging CT examinations for breast cancer in a 51-year-old woman. Laparoscopic resection of the lesion was performed after completion of breast-conserving surgery and whole breast irradiation. The defect of the muscular layer of the esophagus caused by the complete removal of the lesion required repair with muscular sutures. It was helpful to inspect the integrity of the esophageal wall repair by examining the exterior wall of the esophagus laparoscopically while insufflating air into the esophageal lumen through a fiberoptic esophagoscope. A laparoscopic approach utilizing intraoperative esophagoscopy is easy and safe for removal of intra-abdominal esophageal duplication cysts.

Splenic artery embolization using contour emboli before laparoscopic or laparoscopically assisted splenectomy.

The present study assessed preoperative splenic artery embolization using spherical embolic material, super absorbent polymer microspheres (SAP-MS), before laparoscopic or laparoscopically assisted splenectomy. Distal splenic artery embolization using 250 to 400 microm SAP-MS was performed in nine cases with ITP and in seven cases with the other diseases with splenomegaly. Laparoscopic or laparoscopically assisted splenectomies, including a hand-assisted procedure and the procedure involving left upper minilaparotomy, were done 2 to 4 hours after embolization. Conversion to traditional laparotomy was not required in any of the 16 cases, while conversion to 12-cm laparotomy was required in one case with massive splenomegaly. Mean operating time was 161 minutes, and mean intraoperative blood loss was 290 mL. No major postoperative complications were identified, and only one patient reported postembolic pain before surgery. Preoperative splenic artery embolization using painless embolic material, SAP-MS, would be effective for easy and safe laparoscopic or laparoscopically assisted splenectomy.

[TS-1 was prescribed for a patient with stomach cancer with peritoneal dissemination who survived for 3 years and 2 months].

A 42-year-old female patient underwent total gastrectomy for gastric cancer (Borrmann's Type 3). Many rice-grain sized peritoneal metastases were observed in the transverse colon and mesenterium. The lesion was diagnosed as stage IV cancer and the degree of radical cure was determined to be C. Chemotherapy with TS-1 was administered postoperatively. In each cycle, the drug was administered at a daily dose of 100 mg for 4 weeks, followed by a drug-free period of 2 weeks. The adverse reactions were mild, and she underwent the 2nd and further courses of therapy on an outpatient basis. Since she had acute cholecystitis during the 12th course, the drug was withdrawn for 2 months. Thereafter, the drug was started again after resolution of the cholecystitis. At present, ie, 3 years and 2 months after the surgery, the patient is receiving the 23rd course of chemotherapy on an outpatient basis, and abdominal CT shows no evidence of increase in the peritoneal metastases, enlargement of the intraperitoneal lymph nodes, or ascites.

Prognostic factors for gastrectomy in elderly patients.

The decision to undergo surgery for gastric cancer patients aged ≥85 years should be made carefully. We retrospectively reviewed the prognostic factors of gastrectomy for 64 patients aged ≥85 years who had undergone curative gastrectomy for gastric cancer. The effects of various clinical characteristics and surgical interventions on survival were retrospectively analyzed. Univariate analysis revealed that sex (male/female; P = 0.001), the extent of gastric resection (total/distal; P = 0.028), the extent of lymph node dissection (D2/

Gastric neuroendocrine tumors in our institutions according to the WHO 2010 classification.

In 2010, World Health Organization classified gastric neuroendocrine tumor (NET) as follows: NET grade (G) 1, NET G2, neuroendocrine carcinoma (NEC). We reviewed 22 gastric NETs that were encountered in our institutions. Nine, 6, and 4 were NET G1, G2, and NEC, respectively. We also encountered 3 NET G3. NET G1 was treated with observation in 2 patients, endoscopic mucosal resection (EMR) in 3, and gastrectomy in 4 patients. No recurrence was experienced during a median of 53 months of follow-up. All NET G2 was treated with gastrectomy. No patient experienced recurrence during a median of 25 months of follow-up. NET G3 was treated with gastrectomy. One patient died of liver metastasis 52 months after gastrectomy. For NEC, gastrectomy was performed in 3 cases and no patients died of tumor-related death. We conclude that the prognoses of NET G1 and G2 were good. We also experienced long-term survivors of NEC. An accumulation of more patients is needed for further investigation.

Reduced thiamine (vitamin B1) levels following gastrectomy for gastric cancer.

BACKGROUND: Vitamin B1 deficiency is well known as a possible complication following gastric restrictive surgery for morbid obesity; however, reduced vitamin B1 levels in patients who have undergone gastrectomy for gastric cancer have not been discussed previously. METHODS: Serum vitamin B1 levels were determined after the return to normal daily activity in 54 patients with distal gastrectomy for gastric cancer, 32 patients with total gastrectomy for gastric cancer, and 30 patients with radical surgery for colorectal cancer. Changes from serum vitamin B1 levels before operation to those after return to normal daily activity, without nutritional support, were investigated in 25 patients with gastrectomy for gastric cancer and 26 patients with radical surgery for colorectal cancer. RESULTS: Decreased serum vitamin B1 levels, below the normal range, were recognized in 7 of the 54 distally gastrectomized patients and in 5 of the 32 totally gastrectomized patients, whereas no such decrease was recognized in any patient after colorectal surgery. Decreased serum vitamin B1 level was recognized within 6 months after the operation in 6 of the 7 distally gastrectomized patients showing a decreased vitamin B1 level and in 3 of the 5 totally gastrectomized patients showing a decreased vitamin B1 level. Postoperative serum vitamin B1 levels were significantly lower than those before operation in patients with gastrectomies, whereas there was no significant difference in serum vitamin B1 levels before and after the surgeries in patients with surgery for colorectal cancer. CONCLUSION: Vitamin B1 levels may be reduced in gastrectomized patients, especially within 6 months after operation, even after their return to normal daily activity without nutritional support.

Manganese deposition in basal ganglia due to perioperative parenteral nutrition following gastrointestinal surgeries.

BACKGROUND/AIMS: Serial changes in blood manganese (Mn) levels and brain MRI examinations following perioperative parenteral nutrition (PN) were investigated. METHODS: Six cases undergoing pancreatoduodenectomy (PD), 4 cases undergoing thoracic esophagectomy (TE), 18 cases undergoing total gastrectomy (TG) and 20 cases undergoing colorectal surgeries (CR) with daily administration of 20 micromol of Mn per day were studied. Cases undergoing PD, TE, TG or CR without Mn administration served as controls. RESULTS: Hyperintense lesions in the basal ganglia on T1-weighted MRI and elevated blood Mn levels were recognized after PN in 4 of 6 cases in the PD group, in 3 of 4 cases in the TE group, in 1 of 18 cases in the TG group and in 2 of 20 cases in the CR group. No abnormalities were recognized in the control groups. CONCLUSION: The possible Mn deposition in the basal ganglia caused by perioperative PN should be especially noted in cases undergoing PD or TE.

Solitary necrotic nodule of the liver.

Solitary necrotic nodule of the liver is a rare benign lesion; only 22 cases have been reported to date. An unsolved problem in treating these lesions involves the difficulties in differential diagnosis; specific features of necrotic nodule of the liver in preoperative examinations have not been identified. Here, we report a patient with resected solitary necrotic nodule of the liver with preoperative features shown on ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) examinations. A 48-year-old woman was referred to our hospital on December 13, 1999 because a hypoechoic lesion in Couinaud's segment VIII of the liver had been incidentally detected on US. A CT scan confirmed the presence of a round hypodense lesion, measuring 2 cm in diameter. No significant enhancement was recognized on dynamic MRI study. T1-Weighted MRI examinations demonstrated a low intensity showing a triple-layered pattern with low-iso-low intensity in the lesion, while T2-weighted images demonstrated a slightly high intensity in the lesion. These features suggested fibrous tissue. Histological examinations following partial resection of the liver revealed a solitary necrotic nodule of the liver. Combination studies, including MRI examinations, would be useful for the preoperative diagnosis of a solitary necrotic nodule of the liver.