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Purpose: Pancreatic fistula (PF) is the most serious complication following pancreaticoduodenectomy (PD). This study was performed to identify new clinical factors that may predict the development of PF after PD to improve perioperative management., Methods: Seventy-five consecutive patients who underwent PD from 2012 to 2015 were evaluated. The patients' perioperative data including the computed tomography (CT) parameters were collected. The minimum, maximum, and mean CT attenuation values (HU min , HU max , and HU mean , respectively) were extracted from the pancreatic parenchyma (≥ 100 pixels), and the standard deviation of these values (HU SD ) was determined from the slice in which the superior mesenteric and splenic veins were merged. PF was defined as grade B or C according to the International Study Group for Pancreatic Fistula criteria., Results: The PF occurrence rate (grade B or C) was 25.3% in 75 patients. A multivariate analysis identified a larger HU SD (odds ratio 3.092; 95% CI 1.018-9.394) and higher amylase concentration in drainage fluid on postoperative day 1 (odds ratio 1.0001; 95% CI 1.00001-1.00022) as significant risk factors for PF., Conclusions: The HU SD of preoperative CT attenuation values in the pancreatic parenchyma was found to be an independent predictor for PF after PD and it might therefore positively contribute to the perioperative management of PD.

Purpose: Co-signaling molecules play an important role in T cells. This study was designed to investigate PD-1 and Tim-3 expression on T cells and the relationships between PD-1 and Tim-3 expression and immune evasion in patients with gastric cancer., Methods: Using multicolor flow cytometry, we analyzed PD-1 and Tim-3 expression on CD8+ T cells obtained from peripheral blood mononuclear cells (PBMCs) and gastric cancer tissue., Results: Significantly more PD-1+ and Tim-3+ CD8+ T cells in peripheral blood were found in gastric cancer patients than in healthy controls. PD-1+ CD8+ T cells were significantly correlated with Tim-3+ CD8+ T cells in peripheral blood from the gastric cancer patients (r = 0.29, p = 0.036). Furthermore, significantly greater numbers of PD-1+ and Tim-3+ CD8+ T cells were seen in the gastric cancer tissue samples than in the PBMCs. CD8+ T cells positive for both PD-1 and Tim-3 produced significantly less IFN-gamma than cells negative for both and cells positive for PD-1 and negative for Tim-3., Conclusion: An increased number of PD-1+ and Tim-3+ CD8+ T cells is closely related to impaired function of CD8+ T cells in gastric cancer patients.

Purpose: We evaluated prognostic indicators based on inflammatory and nutritional factors, namely, the modified Glasgow Prognostic Score (mGPS), the Prognostic Nutritional Index (PNI), the neutrophil/lymphocyte ratio (NLR), and the platelet/lymphocyte ratio (PLR), to determine their efficiency and significance after pancreaticoduodenectomy for pancreatic cancer., Methods: The subjects of this study were 46 patients who underwent pancreaticoduodenectomy for pancreatic cancer between October 2007 and December 2014. Patients were divided into preoperative mGPS (0/1 and 2), PNI (<40 and ≥40), NLR (<2.5 and ≥2.5), and PLR (<200 and ≥200) groups, to evaluate various perioperative outcomes., Results: Hemoglobin concentrations were significantly lower (P = 0.019), whereas intra-abdominal bleeding was significantly higher (P = 0.040) in the PNI (<40) group than in the PNI (≥40) group. The incidence of postoperative pneumonia was significantly higher in the mGPS (2) group (P = 0.009), and surgical complications greater than grade 3 (Clavien-Dindo classification) were significantly increased in the NLR (≥2.5) group (P = 0.041). Overall survival rates in the PNI (<40) (P = 0.019), NLR (≥2.5) (P = 0.001), and PLR (≥200) (P < 0.001) groups were significantly lower than those in the other groups. The PLR was the only independent prognostic indicator (P = 0.002) according to multivariate analysis., Conclusions: The mGPS, PNI, and NLR were effective predictive indicators of postoperative complications. The PLR was the most useful prognostic indicator for pancreatic cancer patients after pancreaticoduodenectomy.

Purpose: There is accumulating evidence that inflammation is linked to cancer development and progression. Interleukin-17 (IL-17), an inflammatory cytokine, is produced by CD 8+ T cells (Tc17 cells); however, the specific role of Tc17 cells in tumor immunity against gastric cancer remains unclear., Methods: The prevalence of Tc17 cells in both peripheral blood mononuclear cells and gastric tissue was evaluated by multicolor flow cytometry and the concentration of IL-17 in sera was quantitated by an enzyme-linked immunosorbent assay., Results: Circulating Tc17 cells were significantly more numerous in gastric cancer patients than in controls, and significantly more numerous before surgery than after surgery. IL-17 concentrations in gastric cancer patients and healthy controls were 0.51 ± 0.54 and 0.084 ± 0.084 pg/mL, respectively, with this difference being significant. The percentage of Tc17 cells was significantly related to serum IL-17 concentration. Tc17 cells were significantly more numerous than peripheral blood mononuclear cells in gastric cancer tissue. Furthermore, Tc17 cells were more numerous in cancerous gastric tissue than in normal gastric tissue., Conclusions: Tc17 cells may be the main source of IL-17 in gastric cancer patients and thus involved in the progression of gastric cancer.

Purpose: We investigated the relationship between the p53-dependent apoptotic pathway and the survival of patients with gastric cancer, retrospectively, to elucidate new biomarkers of uracil/tegafur (UFT) chemotherapy., Methods: We examined the expression of p53, p21, Bax, and myeloid cell leukemia 1 (Mcl-1) proteins immunohistochemically in 105 patients who underwent curative gastrectomy for gastric cancer invading the serosa. Postoperative oral UFT was prescribed for 1 year. Kaplan-Meier survival curves were compared with the two-sided log-rank test., Results: Positive staining for p53, p21, Bax, and Mcl-1 proteins was found in 63.8, 52.4, 39.0, and 72.4% of the subjects, respectively. Survival time did not differ significantly between the patients with and those without p53, p21, and Bax expression. However, patients with Mcl-1- tumors survived longer than those with Mcl-1+ tumors. Postoperative UFT treatment did not improve survival; however, adjuvant UFT significantly prolonged the survival of patients with p53-, p21-), Bax+, or Mcl-1+ tumors, but not of patients with p53+, p21+, Bax-, or Mcl-1- tumors., Conclusions: The efficacy of adjuvant chemotherapy for gastric cancer may be affected by the status of apoptosis-related proteins such as p53, p21, Bax, and Mcl-1. However, because susceptibility to apoptosis did not explain the sensitivity of chemotherapeutic agents, further investigation of the mutual interaction between apoptosis-related proteins is required.

Irinotecan (CPT-11) is used as a first- and second-line chemotherapy for advanced or recurrent colorectal cancer (CRC). However, only 20%-30% of patients show an objective response to CPT-11 and the drug has severe toxicities, such as delayed-onset diarrhea, neutropenia, nausea, and vomiting. It is important to select patients who will demonstrate sensitivity to CPT-11 treatment to avoid unnecessary drug toxicities and to introduce anticancer treatment benefits to CRC patients. DNA topoisomerase I (Topo I) is essential for vital cellular processes such as DNA replication, transcription, translation, recombination, and repair. This article reviews the possibility of assessing Topo I protein expression in tumors as a biological marker for CPT-11 treatment in CRC.

Purpose: Patients diagnosed with early gastric cancer located in the middle third of the stomach have two major surgical options, namely a conventional distal gastrectomy with Billroth I anastomosis (DG) or a pylorus-preserving gastrectomy (PPG). Pyloruspreserving gastrectomy is thought to have greater functional benefits than DG, but the evaluation of its prognosis and outcome has so far been insufficient., Methods: Between 1997 and 2007, 133 patients were diagnosed with early gastric cancer located in the middle third of the stomach. Distal gastrectomy was performed in 87 and PPG was performed in 46 of these patients. The clinicopathological characteristics were compared between the groups., Results: There were fewer dissected lymph nodes in PPG (mean: 21.9) than in DG (mean: 30.4, P = 0.001). Complications were detected in 16.1% of DG patients and in 6.5% of PPG patients. The occurrence of stasis after PPG (6.5%) was similar to that observed after DG (6.9%). One patient in the DG group died from cancer recurrence, but cancer recurrence was not detected in the PPG group. Although the difference was not significant, the overall 5-year survival rate in the 46 PPG patients (95%) was better than that in the 87 DG patients (86%, P = 0.087)., Conclusions: Pylorus-preserving gastrectomy patients had fewer postoperative complications than DG patients. The long-term follow-up of these patients will clarify the nutritional and prognostic benefits of PPG.

Locally advanced carcinomas arising in the hypopharynx, cervical esophagus, or thyroid are traditionally treated by resection of the hypopharynx and cervical esophagus. Various methods of reconstruction aiming to achieve safety and functionality have been reported, including the myocutaneous flap and the free jejunal graft. With advances in microscopic surgery, the free jejunal transplant is now used dominantly; however, this procedure is not without major risks. In this review we examine the short- and long-term complications of this procedure. We also describe our technique of free jejunal graft reconstruction after pharyngoesophagectomy and total laryngectomy with definitive tracheostomy. We used free jejunal graft reconstruction after resection with hypopharyngeal cancer or thyroid cancers in 22 patients. Twenty-one of these patients acquired a good quality of life, but one died after loss of the jejunal graft. Thus, using a free jejunal graft for reconstruction of the hypopharynx or cervical esophagus can be very useful in improving the quality of life of patients.

The prognosis of patients with scirrhous gastric cancer (SGC) is extremely poor. However, recent advances in therapeutic strategies against SGC, using effective anticancer drugs, have prolonged the survival of patients with SGC. This paper reviews the recent therapeutic outcomes of this type of gastric cancer and introduces a new treatment protocol for SGC.

Purpose: In this study, we evaluated the correlation between the postoperative detection of circulating cancer cells and the risk of recurrence in patients with gastric cancer., Methods: Total RNA was extracted from 1.5 ml of peripheral blood from 59 patients with gastric cancer and 15 patients with cholecystolithiasis (control) before and after operation. Carcinoembryonic antigen (CEA) messenger RNA (mRNA) was used as a probe to detect gastric cancer cells in samples using a real-time reverse transcription-polymerase chain reaction (RT-PCR)., Results: Carcinoembryonic antigen mRNA-positive cells were not found in the peripheral blood of the control patients either before or after operation, nor in the peripheral blood of the gastric cancer patients before operation. However, CEA and mRNA-positive cells were detected in 46% of the patients just after a gastrectomy, though these circulating cancer cells disappeared from peripheral blood within 2 postoperative days. In 55 patients who underwent a curative operation, the risk for cancer recurrence (10/30; 33%) in 30 patients who did not show circulating cancer cells postoperatively was higher than that for cancer recurrence (3/25; 12%) in 25 patients with positive for circulating cancer cells (P = 0.064). As a result, the presence of blood circulating tumor cells just after surgery tends to correlate with a low rate of tumor recurrence in patients operated on for gastric cancer., Conclusion: These findings indicate that a gastrectomy may spread gastric cancer cells into the peripheral blood from primary tumors; however, such circulating cancer cells may be destroyed within a short time. The detection of circulating cancer cells may therefore be a marker for a possibly better prognosis in patients with gastric cancer.

The preoperative levels of serum-soluble receptor for interleukin-2 (IL-2R) were determined by an enzyme-linked immunosorbent assay in 38 patients undergoing surgery for colorectal cancer and 98 healthy controls. The levels of serum-soluble IL-2R in the patients with colorectal cancer were significantly higher than those in the normal controls (P < 0.05). Markedly elevated levels of serum-soluble IL-2R were recognized in patients with stage IV cancer, those with Dukes' stage D cancer, and those with liver metastasis. Moreover, the prognosis of patients with low levels of IL-2R (<531 U/ml) was significantly better than that of those with high levels (P < 0.05). These findings demonstrate that an elevated concentration of soluble IL-2R might be a useful indicator of liver metastasis and poor prognosis in patients with colorectal carcinoma.

We report herein the rare case of a patient who survived for 5 years and 10 months after commencing treatment for gastric cancer with simultaneous disseminated peritoneal metastasis. A 45-year-old man was diagnosed as having advanced gastric cancer following the discovery of numerous nodules in the peritoneal cavity at laparotomy. The patient was treated by palliative gastrectomy and continuous hyperthermic peritoneal perfusion (CHPP) immediately after surgery on November 11, 1987. Postoperatively, he underwent radiofrequency (RF) hyperthermia with intraperitoneal cisplatin a total of seven times. He continued on a combination of uracil and tegafur (UFT) administered orally with a protein-bound beta-D-glucan extracted from the mycelia of Cariolus versicolor (PSK). Long-term survival was achieved following the initial palliative gastrectomy despite simultaneous disseminated peritoneal metastasis.

For patients with gastric cancer and either P1 or P2 peritoneal metastasis, no definite consistent policy with respect to the extent of lymph node dissection has yet been established. In palliatively gastrectomized patients, we analyzed the relationship between the extent of lymphadenectomy and postoperative survival. In patients with P1, an R2 or R3 lymphadenectomy was associated with a significantly improved postoperative survival as compared to an R1 dissection, while this, however, was not the case in patients with P2. As this study was not intended to be a prospective randomized study, a definite conclusion should be avoided. However, our findings suggest that in patients with P1, surgery should not be confined to a resection of the primary lesion, but should also include an R2 or R3 lymphadenectomy.

The multiple occurrence of a single cancer tends to result in the increased vulnerability of some other organs to another malignancy. In the present study, we examined a total of 1,606 patients with gastric cancer to ascertain whether the frequency of second primaries in organs other than the stomach is higher in patients with multiple gastric cancers than in those with a single gastric cancer. Primary cancers of other organs were present in 87 (5.9%) of 1,474 patients with single gastric cancer and in 16 (12.1%) of 132 patients with multiple gastric cancers. The difference was statistically significant. The most frequent site of the occurrence of a second primary was the colo-rectum, followed by the urogenital organs, uterus, breast, and lung in descending order of frequency. We therefore assume that the occurrence of multiple cancers in the stomach is not merely a chance phenomenon but is related to both genetic predisposition and environmental factors.