The relationship between observation interval and prognosis in pancreatic cancer concomitant with intraductal papillary mucinous neoplasia.

BACKGROUND: Intraductal papillary mucinous neoplasia (IPMN) is a risk factor for pancreatic cancer (PC). PC concomitant with IPMN shows rapid progression similar to de novo PC, therefore, the appropriate observation interval (OI) is not yet clear. PATIENTS AND METHOD: This was a multicenter retrospective observational study, and patients with PC concomitant with IPMN were analyzed. OI was defined as the interval between the date of imaging at PC diagnosis and just before the diagnosis. Clinical factors of PC and prognosis were assessed according to OI. RESULTS: From January 2010 to December 2018, 73 patients from 11 institutions were enrolled. The images performed just before PC diagnosis were contrast-enhanced CT/magnetic resonance imaging/endoscopic ultrasonography in 44/27/2 patients, respectively. The median cyst size was 14.0 mm, and the median main pancreatic duct diameter was 3.0 mm. The median OI was 6.8 months. In OI 6 months or less (OI ≤ 6 M)/OI more than 6 months (OI > 6 M), the mean tumor size, the frequencies of metastatic PC, resectable PC and early-stage PC were 20.1/21.5 mm (P = 0.91), 12.1 %/32.5 % (P = 0.05), 72.7 %/52.5 % (P = 0.09) and 27.3 %/25.0 % (P = 1.00), respectively. The median overall survival was 35.5 months in OI ≤ 6 M and 16.2 months in OI > 6 M (P = 0.05). CONCLUSION: In OI 6 months or less, the rate of resectable PC was high, however, the rate of early PC was almost the same as that of OI more than 6 months. Approximately 10 % of cases found in the advanced stage with metastasis even if OI 6 months or less.

Early endpoints of a randomized phase II trial of preoperative chemotherapy with S-1/CDDP with or without trastuzumab followed by surgery for HER2-positive resectable gastric or esophagogastric junction adenocarcinoma with extensive lymph node metastasis: Japan Clinical Oncology Group study JCOG1301C (Trigger Study).

BACKGROUND: This randomized phase II study explored the superiority of trastuzumab plus S-1 plus cisplatin (SP) over SP alone as neoadjuvant chemotherapy (NAC) for HER2-positive resectable gastric cancer with extensive lymph node metastasis. METHODS: Eligible patients with HER2-positive gastric or esophagogastric junction cancer and extensive lymph node metastasis were randomized to receive three or four courses of preoperative chemotherapy with SP (arm A) or SP plus trastuzumab (arm B). Following gastrectomy, adjuvant chemotherapy with S-1 was administered for 1 year in both arms. The primary endpoint was overall survival, and the sample size was 130 patients in total. The trial is registered with the Japan Registry of Clinical Trials, jRCTs031180006. RESULTS: This report elucidates the early endpoints, including pathological findings and safety. The study was terminated early due to slow patient accruals. In total, 46 patients were allocated to arm A (n = 22) and arm B (n = 24). NAC was completed in 20 patients (91%) in arm A and 23 patients (96%) in arm B, with similar incidences of grade 3-4 hematological and non-hematological adverse events. Objective response rates were 50% in arm A and 84% in arm B (p = 0·065). %R0 resection rates were 91% and 92%, and pathological response rates (≥ grade 1b in Japanese classification) were 23% and 50% (p = 0·072) in resected patients, respectively. CONCLUSIONS: Trastuzumab can be safely added to platinum-containing doublet chemotherapy as NAC, and it has the potential to contribute to higher antitumor activity against locally advanced, HER2-positive gastric or esophagogastric junction cancer with extensive nodal metastasis.

Efficacy and survival of nivolumab treatment for recurrent/unresectable esophageal squamous-cell carcinoma: real-world clinical data from a large multi-institutional cohort.

BACKGROUND: Real-world clinical outcomes of and prognostic factors for nivolumab treatment for esophageal squamous-cell carcinoma (ESCC) remain unclear. This study aimed to evaluate real-world outcomes of nivolumab monotherapy in association with relevant clinical parameters in recurrent/unresectable advanced ESCC patients. METHODS: This population-based multicenter cohort study included a total of 282 patients from 15 institutions with recurrent/unresectable advanced ESCC who received nivolumab as a second-line or later therapy between 2014 and 2022. Data, including the best overall response, progression-free survival (PFS), and overall survival (OS), were retrospectively collected from these patients. RESULTS: Objective response and disease control rates were 17.0% and 47.9%, respectively. The clinical response to nivolumab treatment significantly correlated with development of overall immune-related adverse events (P < .0001), including rash (P < .0001), hypothyroidism (P = .03), and interstitial pneumonia (P = .004). Organ-specific best response rates were 20.6% in lymph nodes, 17.4% in lungs, 15.4% in pleural dissemination, and 13.6% in primary lesions. In terms of patient survival, the median OS and PFS was 10.9 and 2.4 months, respectively. Univariate analysis of OS revealed that performance status (PS; P < .0001), number of metastatic organs (P = .019), C-reactive protein-to-albumin ratio (CAR; P < .0001), neutrophil-lymphocyte ratio (P = .001), and PMI (P = .024) were significant. Multivariate analysis further identified CAR [hazard ratio (HR) = 1.61, 95% confidence interval (CI) 1.15-2.25, P = .0053)] in addition to PS (HR = 1.65, 95% CI 1.23-2.22, P = .0008) as independent prognostic parameters. CONCLUSIONS: CAR and PS before nivolumab treatment are useful in predicting long-term survival in recurrent/unresectable advanced ESCC patients with second-line or later nivolumab treatment. TRIAL REGISTRATION: UMIN000040462.

Association between continuous cessation or reduction of drinking alcohol and improvement of multiple dysplastic lesions in patients with esophageal squamous cell carcinoma after endoscopic resection.

BACKGROUND: Multiple development of squamous cell carcinoma (SCC) in the upper aerodigestive tract has been explained by the 'field cancerization phenomenon' associated with alcohol drinking. Squamous dysplastic lesion is clinically visualised as a Lugol-voiding lesion (LVL) by chromoendoscopy. Whether cessation or reduction of alcohol drinking improves multiple LVL and reduces the risk of field cancerization has not been elucidated. METHODS: We analysed 330 patients with newly diagnosed superficial esophageal SCC (ESCC) enrolled in the cohort study. The grade of LVL was assessed in all patients every 6 months. We instructed the patients to stop smoking and drinking and recorded their drinking and smoking status every 6 months. RESULTS: Among 330 patients, we excluded 98 with no LVL or no drinking habit. Of the remaining 232 patients, 158 continuously ceased or reduced their drinking habit. Patients who ceased or reduced their drinking habit significantly showed improvement in the grade of LVL. Multivariate analysis showed that continuous cessation or reduction of drinking habit improved the grade of LVL (hazard ratio [HR] = 8.5, 95% confidence interval [CI] 1.7-153.8, p = 0.0053). Higher grade of LVL carried a high risk of multiple ESCC and head and neck SCC (HNSCC) (HR = 3.7, 95% CI 2.2-6.4, p < 0.0001). Improvement in LVL significantly decreased the risk of multiple ESCC and HNSCC (HR = 0.2, 95% CI 0.04-0.7, p = 0.009). CONCLUSIONS: This is the first report indicating that field cancerization was reversible and cessation or reduction of drinking alcohol could prevent multiple squamous dysplastic lesion and multiple ESCC and HNSCC development. CLINICAL TRIALS REGISTRY NUMBER: UMIN000001676.

Chemoradiotherapy versus triplet chemotherapy as initial therapy for T4b esophageal cancer: survival results from a multicenter randomized Phase 2 trial.

BACKGROUND: We report the long-term results as primary endpoint in a multicentre randomized prospective Phase 2 trial which compared chemoradiotherapy (CRT) and triplet chemotherapy (CT) as the initial therapy for conversion surgery (CS) in T4b esophageal cancer (EC). METHODS: Patients with T4b EC were randomly assigned to the CRT group or CT group as initial treatment. CS was performed if resectable after initial or secondary treatment. The primary endpoint was 2-year overall survival, analysed by intention-to-treat. RESULTS: The median follow-up period was 43.8 months. The 2-year survival rate was higher in the CRT group (55.1%; 95% CI: 41.1-68.3%) compared to the CT group (34.7%; 95% CI: 22.8-48.9%), although the difference was not significant (P = 0.11). Local and regional lymph node recurrence in patients undergoing R0 resection was significantly higher in the CT group compared to the CRT group (local: 30% versus 8%, respectively, P = 0.03; regional: 37% versus 8%, respectively, P = 0.002). CONCLUSIONS: Upfront CT was not superior to upfront CRT as induction therapy for T4b EC in terms of 2-year survival and was significantly inferior to upfront CRT in terms of local and regional control. REGISTRATION: The Japan Registry of Clinical Trials (s051180164).

Three-Course Neoadjuvant Chemotherapy Associated with Unfavorable Survival of Non-responders to the First Two Courses for Locally Advanced Esophageal Cancer.

BACKGROUND: Three-course neoadjuvant chemotherapy (NAC) followed by surgery has become a standard of care for locally advanced esophageal cancer (EC). However, some patients occasionally experience a poor tumor response to the third course and have a poor clinical outcome. METHODS: An exploratory analysis of data from the authors' recent multicenter randomized phase 2 trial compared patients with locally advanced EC who received two courses (n = 78) and those who received three courses (n = 68) of NAC. The association between tumor response and clinico-pathologic factors, including survival, was evaluated to identify risk factors in the three-course group. RESULTS: Of 68 patients who received three courses of NAC, 28 (41.2%) had a tumor reduction rate lower than 10% during the third course. This rate was associated with unfavorable overall survival (OS) and progression-free survival (PFS) compared with a tumor reduction rate of 10% or higher (2-year OS rate: 63.5% vs. 89.3%, P = 0.007; 2-year PFS rate: 52.6% vs. 79.7%, P = 0.020). The independent prognostic factors for OS were tumor reduction rate lower than 10% during the third course (hazard ratio [HR], 2.735; 95% confidence interval [CI] 1.041-7.188; P = 0.041) and age of 65 years or older (HR, 9.557, 95% CI 1.240-73.63; P = 0.030). Receiver operating characteristic curve and multivariable logistic regression analyses identified a tumor reduction rate lower than 50% after the first two courses as an independent predictor of a tumor reduction rate lower than 10% during the third course of NAC (HR, 4.315; 95% CI 1.329-14.02; P = 0.015). CONCLUSION: Continuing NAC through a third course may worsen survival for patients who do not experience a response to the first two courses in locally advanced EC.

Metachronous primary gastric cancer after endoscopic resection in patients with esophageal squamous cell carcinoma.

BACKGROUND: This study aimed to evaluate the risk factors for developing metachronous primary Gastric Cancer (GC) after Endoscopic Resection (ER) for esophageal Squamous Cell Carcinoma (SCC). METHODS: We studied 283 patients with esophageal SCC who underwent ER. The study outcomes were as follows: (1) incidence of metachronous primary GC after ER; and (2) predictors for the development of metachronous primary GC after ER by the Cox proportional hazards model. RESULTS: The median follow-up was 43.1 months (1.81-79.1), and the 3-year cumulative incidence of metachronous primary GC was 6.5% (95%CI: 4.1-10.4). The incidence of metachronous primary GC during the follow-up period was 2.31 per 100 person-years. The frequencies of severe gastric atrophy and macrocytosis at the timing of ER were significantly higher in patients with than without metachronous primary GC (91.7% vs. 73.2%, p = 0.0422, 20.8% vs. 5.2%, p = 0.0046, respectively). Severe gastric atrophy was associated with the development of metachronous primary GC (sex-and-age adjusted hazard ratio (HR) [95%CI] = 4.12 [0.95-27.78], p = 0.0093). Macrocytosis was associated with the development of metachronous primary GC (sex-and-age adjusted HR = 4.76 [1.75-13.0], p = 0.0012) and found to be an independent predictor for metachronous primary GC by multivariate Cox proportional hazards analysis (HR [95%CI] = 4.35 [1.60-11.84], p = 0.004). CONCLUSIONS: Severe gastric atrophy and macrocytosis should be noted in the development of metachronous primary GC after ER for esophageal SCC. In particular, macrocytosis at the timing of ER was considered an important predictor. CLINICAL TRIALS REGISTRY NUMBER: UMIN000001676.

[A Case of Thoracic Esophageal Cancer Treated with COVID-19 Pneumonia during Preoperative Chemoradiotherapy(CRT)].

INTRODUCTION: There is concerned that prognosis of cancer-bearing patients is adversely affected by postponement of cancer treatment due to infection with a new type of coronavirus(COVID-19). We report a case of thoracic esophageal cancer treated with COVID-19 pneumonia during preoperative CRT. A 60-year-old female diagnosed as having Stage Ⅳ thoracic esophageal cancer(cT3N0M1LYM[104R])started receiving preoperative chemoradiotherapy. On the 12th day, she had a fever and was diagnosed with COVID-19 infection. CRT temporarily interrupted and she was treated for COVID-19 pneumonia preferentially. CRT was resumed promptly after remission. Finally, video-Assisted radical esophagectomy was performed. There were no postoperative complications. Nivolumab was started as an adjuvant therapy on the 2nd postoperative months. CONCLUSIONS: We experienced a case of thoracic esophageal cancer in which COVID-19 pneumonia was treated during preoperative CRT, and CRT and surgery were completed without complications by appropriate treatment.

[A Case of Hepatocellular Carcinoma Extending into Right Atrium Was Resected Successfully Using Cardiopulmonary Bypass].

A 59-year-old male was referred to our hospital for a thorough examination of liver function abnormality in the background of chronic hepatitis C. Abdominal contrast-enhanced CT showed multiple tumors in the right lobe of the liver, and an 8 cm tumor occupying S7, a tumor thrombus extending from the right hepatic vein to the inferior vena cava, and a tumor thrombus in the right branch of the portal vein. The patient was diagnosed with hepatocellular carcinoma, cT4N0M0, cStage ⅣA. After 5 courses of hepatic arterial infusion therapy, the intrahepatic lesion was significantly reduced, but micropulmonary metastasis appeared, and the tumor thrombus in the inferior vena cava increased to the thoracic inferior vena cava and just below the tricuspid valve. The patient had difficulty blocking blood flow in the inferior vena cava in the pericardial sac. The patient underwent right hepatectomy, tumor thrombus resection of the inferior vena cava, combined resection of the inferior vena cava, and bovine pericardial patch reconstruction under artificial cardiopulmonary support. He was discharged on the 23rd day after surgery and has been under outpatient observation for 16 months while receiving molecular-targeted drugs for lung metastasis.

[A Case of Long-Term Survival with Multidisciplinary Treatment for Postoperative Local Recurrence of Intrahepatic Cholangiocarcinoma].

We report a case of local recurrence of intrahepatic bile duct cancer that was successfully treated using chemotherapy and radiation therapy. A man in his 80s underwent hepatic resection for intrahepatic cholangiocarcinoma, and abdominal CT 11 months after surgery revealed local recurrence around the dissected surface. He was diagnosed with a local recurrence of intrahepatic cholangiocarcinoma and started systemic chemotherapy(GEM plus CDDP plus S-1). After 11 courses of chemotherapy, stereotactic body radiation therapy(SBRT)was administered to the same site at 50 Gy/10 Fr, as the local recurrence area had increased, although no distant metastases were detected on imaging. The patient was then started on chemotherapy( GEM plus S-1), but after 2 courses, 8 courses of GEM alone were administered at the patient's request. No increase in tumor markers was observed, but an increase in the low-absorption area was observed on imaging. Thereafter, the regimen was changed to S-1. Three months later, the same area was reduced in size and obscured on imaging evaluation. The patient is still taking it 12 months later. No recurrence has been observed since 2 years and 7 months after the start of treatment for local recurrence. This case suggested that multidisciplinary therapy might be useful for local recurrence of intrahepatic cholangiocarcinoma.

[A Case of Conversion Surgery after Long-Term Chemotherapy for Pancreatic Cancer with Peritoneal Metastasis].

A 66-year-old woman was referred to the gastroenterology division of our hospital due to elevation of serum CEA level. Contrast-enhanced CT showed a hypovascular tumor at the body of pancreas. She was diagnosed with pancreatic cancer by EUS-FNA. By laparotomy, we found white nodules on mesentery and abdominal wall, which were diagnosed as peritoneal metastasis. After systemic chemotherapy with 9 courses of gemcitabine(GEM)plus nab-paclitaxel(PTX)and 30 courses of mFOLFIRINOX, the tumor had shrunk and serum CA19-9 level were remarkably decreased. Distal pancreatectomy was performed as conversion surgery. Pathological analysis revealed no remnant cancer cells in the primary tumor or the lymph nodes, confirming a pCR. S-1 was started as adjuvant chemotherapy, and she remains alive without recurrence 8 months after surgery.

[A Case of Sister Mary Joseph's Nodule after Radiation Therapy for Cervical Cancer].

An umbilical metastasis from an internal malignancy is called Sister Mary Joseph's nodule(SMJN)and has a poor prognosis. Herein, we report a case of umbilical metastasis of cervical cancer. A woman in her eighties underwent radiation therapy for cervical cancer(cT3bN0M0, cStage ⅢB). Primary tumor shrank after treatment, suggesting that radiation therapy induced complete response. Two years and 9 months after treatment, the patient presented with umbilical pain. A CT scan showed an umbilical mass near the umbilical hernia. PET-CT demonstrated high accumulation of FDG at the mass, which led to suspicion of umbilical metastasis(SMJN). Although she underwent radical surgery, she died from cancer 8 months after surgery.

[A Case of Conversion Surgery after Chemotherapy for Unresectable Liver Metastasis of Rectal Cancer].

A 50s female was diagnosed as rectal cancer with multiple liver metastases after fecal occult blood scrutiny. Liver metastases were multiple in both lobes and involved the right Glisson's capsule. We determined that the liver metastases were unresectable and initiated FOLFOXIRI plus panitumumab treatment. After 6 courses of chemotherapy, rectal cancer resection was performed. After 12 courses of chemotherapy, the liver metastases which had extensively involved the right Glisson on imaging, shrank until the P7 root was visible. If S7 Glisson could be preserved, the radical resection was planned. If not, associated liver partition and portal vein ligation for staged hepatectomy(ALPPS)was planned. Intraoperatively, it was determined that preservation of S7 Glisson was possible and blood flow preservation in the S7 region was feasible, and an anterior segment hepatic resection(S5-6-8)and lateral segment hepatic partial resection(S2/3)were performed. She was discharged on the 18th day and has been under outpatient observation 12 months after hepatectomy.

[A Case of Recurrent Gastric Cancer with Long-Term Control via Two Resections and Multidisciplinary Treatment Including Nivolumab].

A 78-year-old woman underwent total gastrectomy with distal pancreatectomy and splenectomy for type 3 gastric cancer and a cystic tumor of the pancreas. Her pathological diagnosis was pT4aN3bM0, pStage ⅢC, and HER2-negative. Capecitabine and oxaliplatin was started as an adjuvant therapy, and capecitabine was administered until 1 year postoperatively. Thirteen months after surgery, she had a recurrence in S3 of the liver and underwent liver resection due to solitary metastasis. The postoperative diagnosis was peritoneal dissemination of gastric cancer with invasion of the falciform ligament. S-1 was started postoperatively. Ten months after surgery, she had a recurrence in S3 of the liver and underwent repeated resection. It invaded into the diaphragm and pericardium, and the final diagnosis was recurrent peritoneal dissemination of gastric cancer. After 5 courses of paclitaxel and ramucirumab, nivolumab was started as a fourth-line therapy for the recurrence of the right supraclavicular lymph nodes, bone, and liver. She had some immune-related adverse events(irAE), including hypothyroidism and hypoadrenocorticism, which required management, but she maintained PR more than 2 years after the initiation of the treatment. Multimodality therapies, including repeated resection and nivolumab, were considered to help her long-term survival.

[A Case of Pancreatic Metastasis from Renal Cell Carcinoma 16 Years after Left Nephrectomy].

A 73-year-old woman underwent left nephrectomy for renal cell carcinoma(RCC). The computed tomography(CT)and magnetic resonance imaging(MRI)revealed a 20-mm tumor in the pancreatic tale showing early enhancement in the arterial phase 16 years after surgery. Fluorodeoxyglucose positron emission tomography(FDG-PET)showed slightly uptake (maximum standard uptake value: SUVmax 2.3)and EUS-FNA showed a hyper-vascularized tumor in the pancreatic tail. A single pancreatic metastasis from RCC was diagnosed, and we performed distal pancreatectomy. The histopathological diagnosis was a metastatic pancreatic tumor from RCC. The postoperative course was uneventful and 1 month after surgery, she is alive with no recurrence.

[The Use of Platinum-Based Chemotherapy for Esophageal Cancer Patients with Impaired Renal Function].

INTRODUCTION: The key drugs of first-line chemotherapy for metastatic esophageal cancer are 5-FU and cisplatin(CF). However, the treatment strategy for unfit patients of CF regimen remains controversial. METHODS: Fifty patients who received first-line chemotherapy including platinum-containing drug for metastatic esophageal cancer between 2018-2022 at Osaka National Hospital were analyzed. They were divided into 4 groups according to estimated creatinine clearance(Ccr) at the beginning of the treatment; Group A(over 60 mL/min)31 patients, Group B(50-59 mL/min)12 patients, Group C(30-49 mL/min)5 patients, and Group D(under 30 mL/min)2 patients. The background and treatment outcome data of each group were retrieved retrospectively and compared. RESULTS: Group B, C, D had more elderly patients than Group A. Each Group B, C, D included 1 patient who received FOLFOX regimen. More than half patients in Group B, C, D reduced the dose of CDDP and the initial dose of CDDP was adequately reduced according to Ccr. Group B, C, D had more patients with decreased renal function over Grade 1 than Group A. The clinical response rate was Group A 65%, Group B 42%, Group C 60%, Group D 50%, respectively. There were no patients who ceased the treatment due to adverse events. CONCLUSION: Adequate dose reduction of CF regimen would become more important in the era that only CF regimen can be a partner of immune-checkpoint inhibitor.

[A Case of Radical Resection after Neoadjuvant Chemotherapy for Rectal Cancer with Pelvic Abscess].

A 66-year-old man with a history of frequent diarrhea was diagnosed with rectal cancer with obstruction and a pelvic abscess. Following a transverse colostomy, he was referred to our hospital. The initial diagnosis was rectal cancer(cT4a N1bM0, cStage Ⅲb)and a pelvic abscess due to tumor perforation. To address this condition, we performed neoadjuvant chemotherapy using a combination of 5-fluorouracil, Leucovorin, oxaliplatin, and irinotecan(FOLFOXIRI). Following 6 courses of FOLFOXIRI, the abscess disappeared and no signs of tumor progression and distant metastases were detected. Subsequently, we performed radical resection with D3LD2 lymph node dissection, leading to a pathological diagnosis of ypT3N1aM0, ypStage Ⅲb. The patient then underwent adjuvant chemotherapy with capecitabine and oxaliplatin(CAPOX). No recurrence was observed after 9 months of follow-up.

The impact of weight loss during neoadjuvant chemotherapy on postoperative infectious complications and prognosis in patients with esophageal cancer: exploratory analysis of OGSG1003.

BACKGROUND: Neoadjuvant therapy followed by surgery is the standard treatment for locally advanced esophageal cancers. During neoadjuvant therapy, tumor-induced esophageal stenosis or adverse events often cause weight loss. However, little is known about the effects of weight loss during neoadjuvant therapy on postoperative complications or prognosis. We investigated the association between weight loss during neoadjuvant chemotherapy, postoperative infectious complications, and prognosis. METHODS: Data from OGSG1003, a randomized phase-II trial comparing two regimens of neoadjuvant chemotherapy, cisplatin and fluorouracil plus Adriamycin and cisplatin and fluorouracil plus docetaxel, for locally advanced esophageal squamous cell carcinoma were used. Body weight was measured before neoadjuvant chemotherapy and esophagectomy. Multivariate analysis for infectious complications and prognosis was performed. RESULTS: The study included 134 patients. The median weight loss during neoadjuvant chemotherapy was 2.83% (-2.07% to 6.29%). Postoperative infectious complications were observed in 37 patients who had a significantly higher weight loss during neoadjuvant chemotherapy (5.18% vs. 1.90%, P = 0.002). Multivariate analysis revealed that > 5% of weight loss during neoadjuvant chemotherapy was the only independent factor associated with postoperative infectious complications (odds ratio 2.69, 95% confidence interval 1.12-6.46, P = 0.027). Weight loss during neoadjuvant chemotherapy was significantly associated with worse recurrence-free survival in the univariate analysis (log-rank test, P = 0.002), but this association was marginal in the multivariate analysis (hazard ratio 1.73, 95% confidence interval 0.98-3.08, P = 0.058). CONCLUSIONS: Severe weight loss during neoadjuvant chemotherapy was an independent risk factor for postoperative infectious complications. Weight maintenance during neoadjuvant chemotherapy may reduce the incidence of postoperative infectious complications.

Multicenter randomised trial of two versus three courses of preoperative cisplatin and fluorouracil plus docetaxel for locally advanced oesophageal squamous cell carcinoma.

BACKGROUND: The optimal number of neoadjuvant chemotherapy (NAC) cycles remains to be established for treating oesophageal squamous cell carcinoma (ESCC). We compared two versus three courses of NAC for treating locally advanced ESCC in a multi-institutional, randomised, Phase II trial. METHODS: We randomly assigned 180 patients with locally advanced ESCC at 6 institutions to either two (N = 91) or three (N = 89) courses of DCF (docetaxel 70 mg/m2, cisplatin 70 mg/m2 i.v. on day 1, fluorouracil 700 mg/m2 continuous infusion for 5 days) every 3 weeks, prior to surgery. The primary endpoint was 2-year progression-free survival (PFS) with an intention-to-treat analysis. RESULTS: Patient background parameters were well-balanced. The R0 resection rates were 98.9 and 96.5% in the two- and three-course groups, respectively (P = 0.830). In resected cases, the two- and three-course groups had comparable pN0 rates (P = 0.225) and histological responses (P = 0.898). The 2-year PFS rate was also comparable between the two groups (71.4 vs. 71.1%, P = 0.669). Among subgroups based on baseline characteristics, only patients aged under 65 years old showed a tendency for better survival with the three-course treatment (hazard ratio = 2.612, 95% confidence interval: 1.012-7.517). CONCLUSIONS: Two courses of a DCF regimen showed potential as an optional NAC treatment for locally advanced ESCC. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry of Japan (identification number UMIN 000015788).

Risk Factors for Para-Aortic Lymph Node Metastasis in Esophagogastric Junction Cancer: Results from a Prospective Nationwide Multicenter Study.

BACKGROUND: Several studies have reported a high incidence of metastasis to para-aortic station 16a2lat (no. 16a2lat) among patients with esophagogastric junction (EGJ) cancer. However, the risk factors for no. 16a2lat metastasis are unclear. This study aimed to clarify the risk factors for no. 16a2lat metastasis in patients with EGJ cancer. METHODS: Among 371 prospectively enrolled patients with EGJ cancer, 344 patients who underwent no. 16a2lat lymph node dissection were analyzed. Background factors were compared between the patients with and those without no. 16a2lat metastasis. The association between the histologic status of 10 regional lymph node stations and that of no. 16a2lat metastasis was evaluated. RESULTS: Among the background factors, clinical N2-3 was the only independent risk factor for no. 16a2lat metastasis (odds ratio [OR], 5.90; p = 0.003). The metastasis rate of no. 16a2lat was 11.8% (11/93) for the patients with cN2-3 disease and 2.0% (5/251) for those with cN0-1 disease. The multivariate analysis showed that nos. 2 and 7 metastases were independent risk factors for no. 16a2lat metastasis, with respective ORs of 5.53 (p = 0.018) and 4.00 (p = 0.041). The patients with neither station no. 2 nor no. 7 metastasis did not exhibit no. 16a2lat metastasis, whereas the rate of no. 16a2lat metastasis was 23.7% for the patients with metastases of both stations. CONCLUSIONS: Clinical N2-3 and histologic positivity of station nos. 2 and 7 were independent risk factors for no. 16a2lat metastasis. These findings could potentially assist in determining the indication for no. 16a2lat dissection for patients with EGJ cancer.