Randomized phase II study of chemoradiotherapy with versus without induction chemotherapy for locally advanced pancreatic cancer: Japan Clinical Oncology Group trial, JCOG1106.

BACKGROUND: Chemoradiotherapy is a treatment option for locally advanced pancreatic cancer. However, the efficacy of induction chemotherapy prior to chemoradiotherapy is uncertain. The aim of this randomized, multicentre phase II study is to evaluate the efficacy and safety of chemoradiotherapy with and without induction chemotherapy to determine the significance of induction chemotherapy. METHODS: Patients with locally advanced pancreatic cancer were randomly assigned to the chemoradiotherapy arm (Arm A) or induction chemotherapy followed by the chemoradiotherapy arm (Arm B). Patients in Arm A underwent radiotherapy with concurrent S-1. Patients in Arm B received induction gemcitabine for 12 weeks, and thereafter, only patients with controlled disease underwent the same chemoradiotherapy as Arm A. After chemoradiotherapy, gemcitabine was continued until disease progression or unacceptable toxicity in both arms. The primary endpoint was overall survival. RESULTS: Amongst 102 patients enrolled, 100 were eligible for efficacy assessment. The probability of survival was greater in Arm B in the first 12 months, but the trend was reversed in the following periods (1-year survival 66.7 vs. 69.3%, 2-year survival 36.9 vs. 18.9%). The hazard ratio was 1.255 (95% confidence interval 0.816-1.930) in favour of Arm A. Gastrointestinal toxicity was slightly more frequent and three treatment-related deaths occurred in Arm A. CONCLUSIONS: This study suggested that the chemoradiotherapy using S-1 alone had more promising efficacy with longer-term survival, compared with induction gemcitabine followed by chemoradiotherapy for locally advanced pancreatic cancer. CLINICAL TRIAL REGISTRATION: The study was registered at the UMIN Clinical Trials Registry as UMIN000006811.

Multifocal origin of occupational cholangiocarcinoma revealed by comparison of multilesion mutational profiles.

Recently identified occupational cholangiocarcinoma among printing workers is characterized by chronic bile duct injuries and precancerous or early cancerous lesions at multiple sites of the bile ducts. These observations suggested the potential multifocal carcinogenesis of the disease. We performed whole-exome analysis of multiple lesions, including the invasive carcinomas and precancerous lesions of four occupational cholangiocarcinoma cases. A much higher mutation burden was observed in both the invasive carcinomas (mean 76.3/Mb) and precancerous lesions (mean 71.8/Mb) than in non-occupational cholangiocarcinomas (mean 1.6/Mb). Most somatic mutations identified in 11 of 16 lesions did not overlap with each other. In contrast, a unique trinucleotide mutational signature of GpCpY to GpTpY was shared among the lesions. These results suggest that most of these lesions are multiclonal in origin and that common mutagenic processes, which may be induced by exposure to haloalkanes or their metabolites, generated somatic mutations at different sites of the bile ducts. A similarly high mutation rate had already been identified in the precancerous lesions, implying an increased potential for carcinogenesis throughout the biliary tree. These genomic features support the importance of ongoing close follow-up of the patients as a group at high risk of recurrence.

Human equilibrative nucleoside transporter-1 expression is a predictor in patients with resected pancreatic cancer treated with adjuvant S-1 chemotherapy.

The high expression of human equilibrative nucleoside transporter-1 (hENT1) and the low expression of dihydropyrimidine dehydrogenase (DPD) are reported to predict a favorable prognosis in patients treated with gemcitabine (GEM) and 5-fluorouracil (5FU) as the adjuvant setting, respectively. The expression of hENT1 and DPD were analyzed in patients registered in the JASPAC 01 trial, which showed a better survival of S-1 over GEM as adjuvant chemotherapy after resection for pancreatic cancer, and their possible roles for predicting treatment outcomes and selecting a chemotherapeutic agent were investigated. Intensity of hENT1 and DPD expression was categorized into no, weak, moderate or strong by immunohistochemistry staining, and the patients were classified into high (strong/moderate) and low (no/weak) groups. Specimens were available for 326 of 377 (86.5%) patients. High expression of hENT1 and DPD was detected in 100 (30.7%) and 63 (19.3%) of 326 patients, respectively. In the S-1 arm, the median overall survival (OS) with low hENT1, 58.0 months, was significantly better than that with high hENT1, 30.9 months (hazard ratio 1.75, P = 0.007). In contrast, there were no significant differences in OS between DPD low and high groups in the S-1 arm and neither the expression levels of hENT1 nor DPD revealed a relationship with treatment outcomes in the GEM arm. The present study did not show that the DPD and hENT1 are useful biomarkers for choosing S-1 or GEM as adjuvant chemotherapy. However, hENT1 expression is a significant prognostic factor for survival in the S-1 arm.

Surgery for Pancreatic Neuroendocrine Tumor G3 and Carcinoma G3 Should be Considered Separately.

BACKGROUND: The role of surgery in pancreatic neuroendocrine neoplasm grade 3 (pNEN-G3) treatment remains unclear. We aimed to clarify the role of surgery for pNEN-G3, which has recently been reclassified as pancreatic neuroendocrine tumor-G3 (pNET-G3) and pancreatic neuroendocrine carcinoma-G3 (pNEC-G3), with and without metastases, respectively. METHODS: We analyzed a subgroup of patients from the Japanese pancreatic NEC study, a Japanese multicenter case-series study of pNEN-G3. Pathologists subclassified 67 patients as having pNET-G3 or pNEC-G3 based on morphological features. We compared the overall survival (OS) rates among patients who were grouped according to whether they had undergone tumor-targeted surgery for tumors without (SwoM) or with (SwM) metastases, or non-surgical procedures (NS). RESULTS: Data from 21 patients with pNET-G3 (SwoM, n = 6; SwM, n = 5; NS, n = 10) and 46 patients with pNEC-G3 (SwoM, n = 8; SwM, n = 5; NS, n = 33) were analyzed. OS of patients with pNET-G3 was significantly longer after SwoM and SwM than with NS (p = 0.018 and p = 0.022). In contrast, OS did not significantly differ between either SwoM or SwM and NS (p = 0.093 and p = 0.489) among patients with pNEC-G3. CONCLUSION: The role of surgery should be considered separately for pNET-G3 and pNEC-G3. Although SwoM and SwM can be considered for pNET-G3, caution is advised before considering SwM and SwoM for pNEC-G3.

[A Case of Long-Term Survival after Total Pancreatectomy for Recurrent Pancreatic Cancer in the Remnant Pancreas after Pancreatoduodenectomy].

We report a case of recurrent pancreatic cancer in the remnant pancreas after pancreatoduodenectomy(PD)that was successfully treated by surgical resection. A woman in her 70s who was treated for multiple lung metastases of breast cancer was referred to our hospital because of obstructive jaundice. A low-density area in the pancreas head(19mm in diameter) and dilatation of the main pancreatic duct were observed on abdominal CT. She was diagnosed with pancreatic head cancer and underwent PD. Twenty months after PD, abdominal CT revealed a tumor in the pancreas tail, and she started receiving chemotherapy containing gemcitabine(GEM)for the diagnosis of recurrent pancreatic cancer in the remnant pancreas. Twelve months after the induction of chemotherapy, we performed surgical resection of the tumor(total pancreatectomy). The pathological diagnosis was moderately differentiated adenocarcinoma, which was similar to the primary lesion, and the tumor was confirmed as recurrence of pancreatic cancer. Although she died of multiple lung metastases of breast cancer 62 months after the total pancreatectomy, the recurrence of pancreatic cancer was not observed without adjuvant therapy during that time.

CA19-9 level determines therapeutic modality in pancreatic cancer patients with para-aortic lymph node metastasis.

BACKGROUND: In general, para-aortic lymph node (LN16) metastasis has been considered as a contraindication for pancreatic resection. However, some pancreatic cancer patients with LN16 metastasis have been reported to survive for longer than expected after pancreatectomy. The purpose of this study was to determine whether pancreatic cancer patients with LN16 metastasis might benefit from surgery. METHODS: We retrospectively reviewed 201 consecutive patients with invasive pancreatic ductal adenocarcinoma who underwent surgery at Osaka National Hospital between April 2003 and December 2012. These patients included 22 patients with LN16 metastasis who underwent an extended lymphadenectomy and 25 patients who underwent a palliative surgical biliary and gastric bypass. The clinicopathological data and outcomes were evaluated using univariate and multivariate analyses. RESULTS: The overall survival of the patients with LN16 metastasis was poorer than that of the LN16-negative patients (P = 0.0014). An overall survival analysis of the LN16-positive patients stratified according to the preoperative CA19-9 level showed a significant difference between patients with a low preoperative CA19-9 level (≤360 U/mL) and those with a high preoperative CA19-9 level (>360 U/mL) (P = 0.0301). No significant difference in overall survival of patients was observed between those with LN16 positivity and those who underwent bypass surgery. However, the overall survival of the LN16-positive patients with a CA19-9 level ≤360 U/mL (n = 11) was significantly higher than that of those who underwent bypass surgery (P = 0.0452). CONCLUSION: Surgical resection and extended lymphadenectomy remains an option for pancreatic cancer patients with LN16-positivity whose CA19-9 level is ≤360 U/mL.

[A Case of Peritoneal Dissemination of Metastatic Gastric Cancer with Successful Docetaxel and S-1 Combination Therapy].

Here, we report a long-term survival case treated with docetaxel and S-1 combination therapy(DS therapy)for peritoneal dissemination of gastric cancer. A 58-year-old man was diagnosed with gastric cancer in 2006. Distal gastrectomy, D2 dissec- tion, and RY reconstruction were performed. The pathological diagnosis was gastric cancer, por2, pT3(SS), pN3a(8/27), pStage ⅢB. S -1 monotherapy was administered as an adjuvant chemotherapy for 1 year from 3 months after surgery. Five years after surgery, peritoneal dissemination and bladder recurrence caused rectal stenosis and hydronephrosis. We performed ileostomy and left nephrostomy. DS therapy was started 5 years and 2 months after the initial surgery. A complete clinical remission was observed 2 years and 10 months after starting DS therapy(23 courses). Multiple lymph node metastasis and bone metastasis were confirmed at 5 years and 5 months(57 courses). Even though irinotecan monotherapy was performed for five courses, the bone and lymph node metastasis increased at 5 years and 9 months after starting DS therapy, and the patient died at 69 years of age. DS therapy may be a useful option for peritoneal metastasis of gastric cancer.

Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01).

BACKGROUND: Although adjuvant chemotherapy with gemcitabine is standard care for resected pancreatic cancer, S-1 has shown non-inferiority to gemcitabine for advanced disease. We aimed to investigate the non-inferiority of S-1 to gemcitabine as adjuvant chemotherapy for pancreatic cancer in terms of overall survival. METHODS: We did a randomised, open-label, multicentre, non-inferiority phase 3 trial undertaken at 33 hospitals in Japan. Patients who had histologically proven invasive ductal carcinoma of the pancreas, pathologically documented stage I-III, and no local residual or microscopic residual tumour, and were aged 20 years or older were eligible. Patients with resected pancreatic cancer were randomly assigned (in a 1:1 ratio) to receive gemcitabine (1000 mg/m(2), intravenously administered on days 1, 8, and 15, every 4 weeks [one cycle], for up to six cycles) or S-1 (40 mg, 50 mg, or 60 mg according to body-surface area, orally administered twice a day for 28 days followed by a 14 day rest, every 6 weeks [one cycle], for up to four cycles) at the data centre by a modified minimisation method, balancing residual tumour status, nodal status, and institutions. The primary outcome was overall survival in the two treatment groups, assessed in the per-protocol population, excluding ineligible patients and those not receiving the allocated treatment. The protocol prespecified that the superiority of S-1 with respect to overall survival was also to be assessed in the per-protocol population by a log-rank test, if the non-inferiority of S-1 was verified. We estimated overall and relapse-free survival using the Kaplan-Meier methods, and assessed non-inferiority of S-1 to gemcitabine using the Cox proportional hazard model. The expected hazard ratio (HR) for mortality was 0.87 with a non-inferiority margin of 1.25 (power 80%; one-sided type I error 2.5%). This trial is registered at UMIN CTR (UMIN000000655). FINDINGS: 385 patients were randomly assigned to treatment between April 11, 2007, and June 29, 2010 (193 to the gemcitabine group and 192 to the S-1 group). Of these, three were exlcuded because of ineligibility and five did not receive chemotherapy. The per-protocol population therefore consisted of 190 patients in the gemcitabine group and 187 patients in the S-1 group. On Sept 15, 2012, following the recommendation from the independent data and safety monitoring committee, this study was discontinued because the prespecified criteria for early discontinuation were met at the interim analysis for efficacy, when all the protocol treatments had been finished. Analysis with the follow-up data on Jan 15, 2016, showed HR of mortality was 0.57 (95% CI 0.44-0.72, pnon-inferiority<0.0001, p<0.0001 for superiority), associated with 5-year overall survival of 24.4% (18.6-30.8) in the gemcitabine group and 44.1% (36.9-51.1) in the S-1 group. Grade 3 or 4 leucopenia, neutropenia, aspartate aminotransferase, and alanine aminotransferase were observed more frequently in the gemcitabine group, whereas stomatitis and diarrhoea were more frequently experienced in the S-1 group. INTERPRETATION: Adjuvant chemotherapy with S-1 can be a new standard care for resected pancreatic cancer in Japanese patients. These results should be assessed in non-Asian patients. FUNDING: Pharma Valley Center, Shizuoka Industrial Foundation, Taiho Pharmaceutical.

Prognostic impact of nodal statuses in patients with pancreatic ductal adenocarcinoma.

BACKGROUND: The present study aimed to clarify the prognostic impact of nodal statuses in pancreatic ductal adenocarcinoma (PDAC) after potentially curative pancreatectomy. METHODS: In 110 patients with >10 examined lymph nodes (ELNs), we investigated how nodal statuses were associated with postoperative survival. Nodal statuses included the number of positive LNs (PLNs); the ratio of PLNs to ELNs (lymph node ratio; LNR); and the location of regional LN metastases, classified as group one (peripancreatic area) and group 2 (outside the peripancreatic area). The maximum χ2 value, provided by a Cox proportional hazards model, was used to determine the optimal cutoff value for the number of PLNs and the LNR. RESULTS: The median numbers of ELNs and metastatic LNs were 33 and 2, respectively. Median survival was longer in patients with ≤3 PLNs (37.5 months), LNR <0.11 (36.1 months), and group 1 LN metastases (37.5 months) compared to in patients with ≥4 PLNs (23.7 months), LNR ≥0.11 (23.9 months), and group 2 LN metastases (22.8 months), respectively. Multivariate analyses revealed that all three investigated nodal statuses were independent factors associated with survival: HR of 2.38 and p = 0.0006 for the location of LN metastases, HR of 1.92 and p = 0.0071 for the number of PLNs, and HR of 1.89 and p = 0.010 for the LNR. CONCLUSIONS: Three nodal statuses-the number of PLNs, the LNR, and the location of LN metastases-could stratify postoperative survival among PDAC patients with an adequate number of examined LNs after pancreatectomy.

Effectiveness of a preoperative exercise and nutritional support program for elderly sarcopenic patients with gastric cancer.

We established a preoperative exercise and nutritional support program for elderly sarcopenic patients with gastric cancer. Twenty-two gastric cancer patients aged 65 years or older with a diagnosis of sarcopenia according to the algorithm proposed by the European Working Group on Sarcopenia in Older People received our preoperative program. The median duration of the program participation was 16 days. Total calorie and protein intakes were significantly higher after the program than before [29.4 ± 6.9 kcal/kg ideal body weight (IBW) vs 27.3 ± 5.6 kcal/kg IBW, p = 0.049, and 1.3 ± 0.4 g/kg IBW vs 1.1 ± 0.3 g/kg IBW, p = 0.0019, respectively]. Handgrip strength significantly increased after the program (21.2 ± 5.2 kg vs 20.0 ± 5.3 kg, p = 0.022). Likewise, gait speed and skeletal muscle mass index increased, although the differences did not reach statistical significance. Four patients became nonsarcopenic after the program. Postoperative complications were observed in three patients (13.6%); however, none of these complications were severe (Clavien-Dindo grade III or lower). A preoperative exercise and nutritional support program has the potential to reduce sarcopenia and improve postoperative outcome in elderly sarcopenic patients with gastric cancer.

The PD-1/PD-L1 axis may be aberrantly activated in occupational cholangiocarcinoma.

An outbreak of cholangiocarcinoma in a printing company was reported in Japan, and these cases were regarded as an occupational disease (occupational cholangiocarcinoma). This study examined the expression status of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) in occupational cholangiocarcinoma. Immunostaining of PD-1, PD-L1, CD3, CD8, and CD163 was performed using tissue sections of occupational cholangiocarcinoma (n = 10), and the results were compared with those of control cases consisting of intrahepatic (n = 23) and extrahepatic (n = 45) cholangiocarcinoma. Carcinoma cells expressed PD-L1 in all cases of occupational cholangiocarcinoma, whereas the detection of PD-L1 expression in cholangiocarcinoma cells was limited to a low number of cases (less than 10%) in the control subjects. In cases of occupational cholangiocarcinoma, occasional PD-L1 expression was also noted in precancerous/preinvasive lesions such as biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct. Additionally, tumor-associated macrophages and tumor-infiltrating T cells expressed PD-L1 and PD-1, respectively. The number of PD-L1-positive mononuclear cells, PD-1-positive lymphocytes, and CD8-positive lymphocytes infiltrating within the tumor was significantly higher in occupational cholangiocarcinoma compared with that in control cases. These results indicate that immune escape via the PD-1/PD-L1 axis may be occurring in occupational cholangiocarcinoma.

[A Case of Long-Term Survival of Recurrent Bile Duct Cancer with Peritoneal Metastasis Successfully Treated with Surgical Resection].

We report a case of peritoneal metastasis of bile duct cancer that was successfully treated by surgical resection. A 70s man underwent pancreatoduodenectomy(PD)for bile duct cancer, and abdominal CT revealed a tumor in the peritoneum along the right kidney at 55 months after PD. As FDG uptake was seen at the lesion on PET-CT, he was diagnosed as recurrence of bile duct cancer or primary malignant tumor in the retroperitoneum. Because the tumor was solitary on CT and PET-CT, we conducted surgical resection of the tumor. Pathological diagnosis was well differentiated adenocarcinoma that was similar to the primary lesion, and the tumor was confirmed as recurrence of bile duct cancer. He remains alive without 2nd recurrence for 60 months since tumor resection(117 months since PD).

[A Case of Duodenum Neuroendocrine Tumor with Multiple Liver Metastasis Treated with Multimodal Therapy].

The patient is a 65-year-old woman with anemia. The multiple liver tumors detected by ultrasonography, it was diagnosed as neuroendocrine tumor(NET), G2 by biopsy. There was an ulcer at the bulb of the duodenum, so we diagnosed liver metastasis of duodenum NET. Because the liver tumors spreaded to both right and left lobes, we carrying out a transcatheter arterial embolization(TAE)twice to liver metastasis, and chemotherapy by octreotide was performed. 20 months after the beginning of treatment, a 4 cm tumor was remained in the left lobe but others were not detected by computed tomography, so we performed cytoreductive surgery. Duodenum bulb resection and left hepatectomy was performed and the specimens were NET, G2 in the pathological findings. We detected a lot of tumors less than 1 cm in the right lobe during the operation, so TAE was carried out for the right lobe after surgery. The disease showed no progression for 28 months after the first admission(post operation5 months).

[A Case of Anal Canal Cancer with Skin Invasion to Which Abdominoperineal Resection and Perineum Reconstruction Were Performed after Neoadjuvant Chemoradiotherapy].

A 74-year-old man visited our hospital with an awareness of anal mass and bleeding. He was diagnosed as adenocarcino- ma of anal canal with wide spreading skin invasion. After neoadjuvant chemoradiotherapy(radiationtotal 45 Gy/25 Fr; cape- citabine 825mg/m2)was performed to reduce the mass volume, laparoscopic abdominoperineal resection with large perineum skin resection and lateral lymph node dissection was carried out. The perineal defect was repaired with a rectus abdominis musculocutaneous flap. Six days after surgery, the rectus abdominis musculocutaneous flap necrotized, and second perineum reconstruction by the bilateral gracilis musculocutaneous flaps was performed after debridement of necrotic tissue. We reported a case of radical resection of local advanced anal canal cancer with skin invasion by performing combined modality therapy and perineum reconstruction.

[Gastrectomy with Intra-Aortic Balloon Pumping Support for a Hemorrhagic Advanced Gastric Cancer Patient with Severe Coronary Stenosis].

Here we report a case of a hemorrhagic gastric cancer patient with severe coronary artery disease, in whom the cancer was successfully resected with the support of intra-aortic balloon pumping(IABP). An 80-year-old man was referred to our hospital for further examination of his anemia and tumor around the pancreatic head. He was diagnosed with type 3 gastric cancer with multiple bulky lymph node metastases invadingto the pancreas(cT4b[LN-Panc], N3a, M1[LYM No.16a2int], cStage IV ). Tarry stools continued and blood transfusion was repeatedly required. To control tumor bleeding, we considered that gastrectomy should be performed prior to chemotherapy. Since he had a history of acute myocardial infarction, coronary angiography was performed, which showed severe coronary stenosis in 3 vessels. Preoperative percutaneous coronary intervention or coronary artery bypass grafting were inappropriate because of tumor bleeding. We performed palliative distal gastrectomy under the support of IABP. The postoperative course was uneventful and he could initiate subsequent chemotherapy smoothly. IABP may be a useful option for hemorrhagic gastric cancer patients with severe coronary stenosis.

Hypermutation and unique mutational signatures of occupational cholangiocarcinoma in printing workers exposed to haloalkanes.

Cholangiocarcinoma is a relatively rare cancer, but its incidence is increasing worldwide. Although several risk factors have been suggested, the etiology and pathogenesis of the majority of cholangiocarcinomas remain unclear. Recently, a high incidence of early-onset cholangiocarcinoma was reported among the workers of a printing company in Osaka, Japan. These workers underwent high exposure to organic solvents, mainly haloalkanes such as 1,2-dichloropropane (1,2-DCP) and/or dichloromethane. We performed whole-exome analysis on four cases of cholangiocarcinoma among the printing workers. An average of 44.8 somatic mutations was detected per Mb in the genome of the printing workers' cholangiocarcinoma tissues, approximately 30-fold higher than that found in control common cholangiocarcinoma tissues. Furthermore, C:G-to-T:A transitions with substantial strand bias as well as unique trinucleotide mutational changes of GpCpY to GpTpY and NpCpY to NpTpY or NpApY were predominant in all of the printing workers' cholangiocarcinoma genomes. These results were consistent with the epidemiological observation that they had been exposed to high concentrations of chemical compounds. Whole-genome analysis of Salmonella typhimurium strain TA100 exposed to 1,2-DCP revealed a partial recapitulation of the mutational signature in the printing workers' cholangiocarcinoma. Although our results provide mutational signatures unique to occupational cholangiocarcinoma, the underlying mechanisms of the disease should be further investigated by using appropriate model systems and by comparison with genomic data from other cancers.

Prognostic and predictive value of extended RAS mutation and mismatch repair status in stage III colorectal cancer.

The prognostic and predictive value of KRAS gene mutations in stage III colorectal cancer is controversial because many recent clinical trials have not involved a surgery-alone arm. Additionally, data on the significance of extended RAS (KRAS/NRAS) mutations in stage III cancer are not available. Hence, we undertook a combined analysis of two phase III randomized trials, in which the usefulness of adjuvant chemotherapy with tegafur-uracil (UFT) was evaluated, as compared with surgery alone. We determined the association of extended RAS and mismatch repair (MMR) status with the effectiveness of adjuvant chemotherapy. Mutations in KRAS exons 2, 3, and 4 and NRAS exons 2 and 3 were detected by direct DNA sequencing. Tumor MMR status was determined by immunohistochemistry. Total RAS mutations were detected in 134/304 (44%) patients. In patients with RAS mutations, a significant benefit was associated with adjuvant UFT in relapse-free survival (RFS) (hazard ratio = 0.49; P = 0.02) and overall survival (hazard ratio = 0.51; P = 0.03). In contrast, among patients without RAS mutations, there was no difference in RFS or overall survival between the adjuvant UFT group and surgery-alone group. We detected deficient DNA MMR in 23/304 (8%) patients. The MMR status was neither prognostic nor predictive for adjuvant chemotherapy. An interaction analysis showed that there was better RFS among patients treated with UFT with RAS mutations, but not for those without RAS mutations. Extended RAS (KRAS/NRAS) mutations are proposed as predictive indicators with respect to the efficacy of adjuvant UFT chemotherapy in patients with resected stage III colorectal cancer.

Prognostic impact of preoperative NLR and CA19-9 in pancreatic cancer.

BACKGROUND: Recently, several preoperative proinflammatory markers and nutritional factors such as neutrophil-to-lymphocyte ratio (NLR) and prognostic nutrition index (PNI) have been reported as significant predictor for poor prognosis of various malignant tumors. In this study, we evaluated the prognostic values of these preoperative parameters in patients with resectable pancreatic head cancer. METHODS: We retrospectively reviewed consecutive patients who underwent PD for pancreatic head cancer between 2007 and 2012. A total of 46 patients were enrolled in this analysis. Preoperative parameters such as CRP, CA19-9, NLR and PNI at the time of presentation were recorded as well as overall survival. Cancer specific survival was assessed using Kaplan-Meier method. Univariate and multivariate Cox regression models were applied to evaluate the prognostic relevance of preoperative parameters. The correlations between CA19-9 values, NLR and pathological findings, first recurrence site were respectively reviewed. RESULTS: In multivariable analysis preoperative high NLR (≧2.7) and high CA19-9 (≧230) were independent prognostic factors for poor survival (P value: 0.03 and 0.025, respectively). Kaplan-Meier survival analysis demonstrated the overall 2-year survival rate in patients with high NLR or high CA19-9 were 37.5% compared with 89.9% in patients with low NLR and low CA19-9. CONCLUSION: Preoperative NLR and serum CA19-9 offer significant prognostic information associated with overall survival following PD in the patients with pancreatic head cancer.

Sarcopenia is associated with severe postoperative complications in elderly gastric cancer patients undergoing gastrectomy.

BACKGROUND: Malignancy is a secondary cause of sarcopenia, which is associated with impaired cancer treatment outcomes. The aim of this study was to investigate the prevalence of preoperative sarcopenia among elderly gastric cancer patients undergoing gastrectomy and the differences in preoperative dietary intake and postoperative complications between sarcopenic and non-sarcopenic patients. METHODS: Ninety-nine patients over 65 years of age who underwent gastrectomy for gastric cancer were analyzed. All patients underwent gait and handgrip strength testing, and whole-body skeletal muscle mass was measured using a bioimpedance analysis technique based on the European Working Group on Sarcopenia in Older People (EWGSOP) algorithm for the evaluation of sarcopenia before surgery. Preoperative dietary intake was assessed using a food frequency questionnaire. RESULTS: Of these patients, 21 (21.2 %) were diagnosed with sarcopenia. Sarcopenic patients consumed fewer calories and less protein preoperatively (23.9 vs. 27.8 kcal/kg ideal weight/day and 0.86 vs. 1.04 g/kg ideal weight/day; P = 0.001 and 0.0005, respectively). Although the overall incidence of postoperative complications was similar in the two groups (57.1 % vs. 35.9 %; P = 0.08), the incidence of severe (Clavien-Dindo grade ≥ IIIa) complications was significantly higher in the sarcopenic group than in the non-sarcopenic group (28.6 % vs. 9.0 %; P = 0.029). In the multivariate analysis, sarcopenia alone was identified as a risk factor for severe postoperative complications (odds ratio, 4.76; 95 % confidence interval, 1.03-24.30; P = 0.046). CONCLUSIONS: Preoperative sarcopenia as defined by the EWGSOP algorithm is a risk factor for severe postoperative complications in elderly gastric cancer patients undergoing gastrectomy.

[A Case of Subacute Thyroiditis during Chemotherapy after Distal Pancreatectomy].

A 68-year-old woman who underwent distal pancreatectomy combined with resection of the celiac axis had an abdominal wall recurrence and resection 2 years after the first surgery. She was treated with S-1 at an outpatient clinic following the surgery. She returned to the clinic with a high fever after the S-1 administration and was diagnosed with febrile neutropenia. However, treatment for febrile neutropenia including antibiotics and G-CSF did not improve her symptoms. Her history of chronic severe neck pain and painful enlargement of her thyroid gland suggested thyroiditis. After blood tests and thyroid scintigraphy, she was diagnosed with subacute thyroiditis and was treated with prednisolone. Her symptoms improved within a week. Although patients with neutropenia and a high fever during chemotherapy are likely to have febrile neutropenia, the possibility of another cause of neutropenia with fever should be considered if treatments for febrile neutropenia are not effective.