[A Case of Hilar Cholangiocarcinoma Arising during Long-Term Follow-Up of Hepatolithiasis].

A 91-year-old man had a history of cholecystectomy and choledochostomy for cholecystolithiasis and choledocholithiasis. Eleven years earlier, intrahepatic stones were found in the posterior bile duct, and he did not wish to undergo treatment. Over time, worsening of the intrahepatic stones and dilation of the intrahepatic bile duct were observed. At 91 years old, enhanced abdominal CT revealed wall thickening of the hilar bile duct, and MRCP showed stenosis of the hilar bile duct. Endoscopic retrograde cholangiography showed no contrast in the right intrahepatic bile duct and marked dilation of the left intrahepatic bile duct. Brush cytology confirmed adenocarcinoma, leading to a diagnosis of hilar cholangiocarcinoma. He underwent open right and caudal lobectomy with biliary reconstruction. Histopathological examination revealed a hilar cholangiocarcinoma, T3N1M0, Stage Ⅲc, mainly located at the confluence of the right and left hepatic ducts. This case suggests a potential association between hepatolithiasis and hilar cholangiocarcinoma, emphasizing the importance of regular imaging examinations for timely surgical resection. Early intervention, including liver resection, is recommended for the management of hepatolithiasis.

[Long-Term Complete Response by CapeOX plus Nivolumab Chemotherapy for Postoperative Recurrence of Gastric Cancer-A Case Report].

A 73-year-old man underwent upper gastrointestinal endoscopy during a medical check-up that revealed a Type 2 lesion in the anterior wall of the gastric body. The biopsy confirmed tub2. A contrast-enhanced CT scan revealed focal wall thickening and lymphadenopathy in the gastric body. The patient was diagnosed with gastric cancer(M, ante, Type 2, T4aN1M0, Stage ⅢA). Laparotomy total gastrectomy D2 dissection and Roux-en-Y reconstruction were performed. Pathological results were tub1, int, INF b, ly0, v1, pT4aN0M0, pStage ⅡB. S-1(100 mg/day)was started as adjuvant chemotherapy but discontinued after 3 courses due to anorexia(Grade 2). Multiple pulmonary metastases(both lungs, 5)were confirmed by CT examination 9 months after the operation. A diagnosis of gastric cancer recurrence was made, and CapeOX plus nivolumab was started as first-line therapy. After 2 courses, lung metastases tended to shrink. The lesion developed a complete response(CR)after 3 months. After that, CapeOX plus nivolumab was continued, but peripheral neuropathy(Grade 2)was observed in the 15th course. With continued capecitabine monotherapy and nivolumab(impaired liver function [Grade 3]for irAE), despite the maintenance of CR, hepatic function increased repeatedly(Grade 3)and led to the discontinuation of chemotherapy upon patient's request. Currently, CR has been maintained for 5 years and 6 months after recurrence.

[A Case of Repeat Pancreatectomy-Robotic Spleen-Preserving Distal Pancreatectomy after Robotic Pancreaticoduodenectomy].

Laparoscopic pancreaticoduodenectomy has been covered by insurance since 2016 in Japan, and advance laparoscopic and robotic pancreaticoduodenectomy has been also covered by insurance since 2020 in Japan. It has been reported that laparoscopic pancreatectomy causes few postoperative adhesions in the abdominal cavity and that repeat laparoscopic surgery could be performed. However, in robotic pancreatectomy, there have been no such reports yet. We reported that even after robotic pancreaticoduodenectomy, there were few adhesions in the abdominal cavity, and we were able to perform the robotic distal pancreatectomy with preservation of the splenic artery and vein. This suggested that robotic surgery was an effective treatment method for repeat pancreatectomy, given its low invasiveness and minimal adhesion.

[A Case of Conversion Surgery for Stage â £ ATP-Producing Gastric Cancer with Distant Metastasis].

We report a case in which a patient with advanced gastric cancer with liver metastasis and bulky N showed marked tumor shrinkage with chemotherapy, and underwent conversion surgery. A 77-year-old male. Patient was referred to our department because of advanced gastric cancer. Upper gastrointestinal endoscopy revealed type 2 advanced cancer in the posterior wall of the gastric antrum. Abdominal CT showed thickening of the gastric wall in the same region and bulky lymph node enlargement and para-aortic lymphadenopathy behind the stomach. Staging laparoscopy showed the primary tumor and bulky lymph nodes forming a single mass, invading the pancreas, jejunum, and mesentery, and a solitary mass in the hepatic S3. Biopsy pathology revealed adenocarcinoma. We diagnosed the advanced gastric cancer cT4b(pancreas, jejunum), N2M1 (LYM, HEP), P0CY0, Stage ⅣB. After 2 courses of systemic chemotherapy FOLFOX/nivolumab, total gastrectomy, D2 node dissection, splenectomy pancreas tail resection, cholecystectomy, hepatic resection, partial transverse colon resection, partial jejunum resection, Roux-en-Y reconstruction. R0 resection was performed. The operative time was 620 minutes and blood loss was 1,025 mL. Pathologically, the patient was diagnosed with hepatoid adenocarcinoma, ypT4bN1M1(LYM, HEP), ypStage Ⅳ. The pathological efficacy evaluation was Grade 1a in the primary tumor. The patient has been recurrence-free for 9 months since the initial diagnosis.

Clinical Impact of Conversion Surgery After Induction Therapy for Esophageal Cancer with Synchronous Distant Metastasis: A Multi-institutional Retrospective Study.

BACKGROUND: The standard treatment for advanced esophageal cancer with synchronous distant metastasis is systemic chemotherapy or immunotherapy. Conversion surgery is not established for esophageal cancer with synchronous distant metastasis. This study aimed to investigate the clinical impact of conversion surgery for esophageal cancer with synchronous distant metastasis after induction therapy. METHODS: This multi-institutional retrospective study enrolled 66 patients with advanced esophageal cancer, including synchronous distant metastasis, who underwent induction chemotherapy or chemoradiotherapy followed by conversion surgery between 2005 and 2021. Short- and long-term outcomes were investigated. RESULTS: Distant lymph node (LN) metastasis occurred in 51 patients (77%). Distant organ metastasis occurred in 15 (23%) patients. There were 41 patients with metastatic para-aortic LNs, and 10 patients with other metastatic LNs. Organs with distant metastasis included the lung in seven patients, liver in seven patients, and liver and lung in one patient. For 61 patients (92%), R0 resection was achieved. The postoperative complication rate was 47%. The in-hospital mortality rate was 1%, and the 3- and 5-year overall survival (OS) rates for all the patients were 32.4% and 24.4%, respectively. The OS rates were similar between the patients with distant LN metastasis and the patients with distant organ metastasis (3-year OS: 34.9% vs. 26.7%; P = 0.435). Multivariate analysis showed that pathologic nodal status is independently associated with a poor prognosis (hazard ratio, 2.43; P = 0.005). CONCLUSIONS: Conversion surgery after chemotherapy or chemoradiotherapy for esophageal cancer with synchronous distant metastasis is feasible and promising. It might be effective for improving the long-term prognosis for patients with controlled nodal status.

Minimally invasive liver resection for cholangiolocellular carcinoma: A single-institution experience.

INTRODUCTION: Cholangiolocellular carcinoma (CoCC) resembles cholangiocellular carcinoma (CCC) and presents a variety of imaging findings; thus, preoperative diagnosis is often difficult. METHODS: We retrospectively studied patients who were diagnosed with CoCC at the Kansai Rosai Hospital from 2006 to 2021 and treated by laparoscopic liver resection (LLR) or open liver resection (OLR). RESULT: Among 918 liver resections, 15 patients were diagnosed with CoCC: 11 underwent LLR and 4 OLR. For LLR and OLR, respectively, patient age was 69.9 ± 6.8 and 72.8 ± 10.6, sex was M/F: 10/1 and 2/2, Child-Pugh was A/B/C: 10/1/0 and 4/0/0, liver damage was A/B/C: 8/3/0 and 4/0/0, preoperative diagnosis was CoCC/CCC/HCC: 1/2/8 and 2/2/0, pathological stage of Union for International Cancer Control (UICC) was IA/IB/II/IIIA/IIIB/IV: 8/0/2/1/0/0 and 0/0/3/0/1/0 (p = .0312), and extent of liver resection was Hr0/HrS/Hr1/Hr2/: 3/0/5/3 and 1/1/0/2. In LLR and OLR, respectively, operation time was 417.5 ± 191.0 and 407.5 ± 187.9 min, blood loss was 123.3 ± 217.4 and 1385.0 ± 1038.7 mL, and postoperative hospital stay was 12.2 ± 13.7 and 15.0 ± 6.6 days. For stages I and II/III, respectively, the 5-year disease-free survival rates were 100.0% and 34.3%, and the 5-year overall survival rates were 100.0% and 55.6%. For stage II/III LLR and OLR, respectively, the 3-year disease-free survival rates were 33.3% and 37.5% (p = .8418), and the 5-year overall survival rates were 66.7% and 50.0% (p = .8084). CONCLUSION: Although further studies are still needed to confirm, minimally invasive liver resection without lymph node dissection is one of a safe and effective approach to the management of CoCC.

Successful treatment of an anastomotic leakage after total gastrectomy using a fully covered self-expandable metal stent with an anchoring thread: A case report.

INTORODUCTION AND IMPORTANCE: The incidence of anastomotic leakage in the esophagojejunostomy after total gastrectomy is a serious complication of this procedure. Here, we report a case in which a fully covered stent was endoscopically placed into a fistula caused by anastomotic leakage after total gastrectomy. CASE PRESENTATION: An 88-year-old man diagnosed with advanced gastric cancer had tumor invasion close to the esophagogastric junction. We performed a laparoscopic total gastrectomy and Roux-en-Y reconstruction. On postoperative day (POD) 3, the patient experienced septic shock due to anastomotic leakage and subsequent mediastinitis. Mediastinal irrigation and drainage under laparotomy were performed. Sepsis improved with drainage, but the fistula persisted due to anastomotic leakage. CLINICAL DISCUSSION: Based on a diagnosis of refractory fistula, a fully covered self-expandable metal stent (HANAROSTENT® Esophagus) was inserted POD 21 using esophagoscopy. To prevent stent migration, a 3-0 silk thread was attached to the ostial side of the stent and fixed at the nose. The stent was endoscopically removed 36 days. Esophagoscopy after stent removal revealed that the fistula had resolved and that the anastomotic leakage had healed. The patient started oral intake and was discharged home. CONCLUSION: This case demonstrates the potential for use of a fully covered self-expandable metal stent with an anchoring thread for anastomotic leakage after total gastrectomy for gastric cancer.

Clinicopathological characteristics and survival outcomes in patients with advanced esophageal squamous cell carcinoma who were intraoperatively diagnosed non-curative.

INTRODUCTION: Curative esophagectomy is not always possible in patients with locally advanced esophageal cancer. However, few studies have investigated patients who underwent non-curative surgery with intraoperative judgment. This study aimed to investigate patient characteristics and clinical outcomes for patients undergoing non-curative surgery and compare them between non-resectional and non-radical surgery. METHODS: Among 989 consecutive patients with thoracic esophageal squamous cell carcinoma (ESCC) who were preoperatively expected for curative esophagectomy, 66 who were eligible for non-curative surgery were included in this study. RESULTS: Intraoperative diagnosis of T4b accounted for 93% of the reasons for the failure of curative surgery. In those patients, esophageal cancer locally invaded into the aortobronchial constriction (70%), trachea (25%), or pulmonary vein (5%). LN metastasis mainly invaded into the trachea (50%), or bronchus (28%).The overall survival of patients with non-curative surgery was 51.5%, 25.7%, and 10.4% at 6, 12, and 24 months after surgery, respectively. Although there were no differences in preoperative patient characteristics between non-resectional and non-radical surgery, distant metastasis, especially pleural dissemination, was significantly observed in T4b patients due to esophageal cancer with non-radical surgery than those with non-resectional surgery (35% vs. 15%, P=0.002). Even in patients with non-curative surgery, R1 resection and postoperative CRT were identified as independent factors for survival 1 year after surgery (P=0.047, and 0.019). CONCLUSIONS: T4b tumor located in aortobronchial constriction or trachea/bronchus makes it difficult to diagnose whether it is resectable or unresectable. Moreover, surgical procedures and perioperative treatment were deeply associated with the clinical outcomes.

Clinical Impact of Enhanced Recovery After Esophagectomy in Patients With Esophageal Cancer.

BACKGROUND/AIM: The enhanced recovery after surgery (ERAS) program is expected to improve perioperative outcomes in patients with esophageal cancer. However, how ERAS impacts the postoperative body composition and factors related to compliance rate of ERAS have not been fully investigated. PATIENTS AND METHODS: The study included 252 consecutive patients with thoracic esophageal cancer who underwent minimally invasive esophagectomy. We compared the postoperative outcomes including body composition between the old perioperative program and the new one that aimed to shorten postoperative length of stay (LOS). Compliance-related clinical factors were also examined. RESULTS: From 252 patients, 129 underwent the old program and 123 the new program. Postoperative LOS, postoperative complications, and hospital costs were reduced with the new program. Body weight loss was significantly improved with the new program at discharge and 3-months after esophagectomy (94.9% vs. 96.6%, p=0.013, 89.5% vs. 91.1%, p=0.028, respectively). Patients in the new program had better body composition at discharge than those in the old program [body fat mass (91.6% vs. 94.1%), lean body mass (95.2% vs. 97.2), and skeletal muscle mass (95.3% vs. 97.0%)]. Major reasons for incompliance were dysphagia, pneumonia, and anastomotic leakage. Multivariate analysis revealed that age ≥70 years at surgery and sex (male) were independent risk factors for incompliance with the postoperative program. CONCLUSION: The new ERAS program aimed to shorten postoperative LOS had clinical benefits in body composition early after esophagectomy. Personalized ERAS programs based on age might lead to better postoperative outcomes because of low compliance rates for older patients.

Usefulness of blood flow evaluation by indocyanine green fluorescence in laparoscopic or robot-assisted surgery for colorectal cancer with persistent descending mesocolon.

A persistent descending mesocolon is defined as a congenital fixation anomaly caused by the defective membrane fusion of the descending colon and the lateral abdominal wall. Anatomically, in persistent descending mesocolon, the left colonic artery is often shortened, and joins the marginal artery soon after its bifurcation from the inferior mesenteric artery, while the colonic mesentery often adheres firmly to the mesentery of the small intestine. As a result of these characteristics, anatomical knowledge of the persistent descending mesocolon and preservation of bowel blood flow are important during surgery for left-sided colorectal cancer to avoid adverse events. Moreover, indocyanine green based blood flow assessment is useful for the detailed evaluation of bowel ischemia at the anastomotic site. Here we report the usefulness of blood flow evaluation using indocyanine green fluorescence in laparoscopic or robot-assisted surgery for three patients with colorectal cancer and persistent descending mesocolons.

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.

Gut microbiota associated with the mitigation effect of synbiotics on adverse events of neoadjuvant chemotherapy in patients with esophageal cancer: A retrospective exploratory study.

Introduction. Our synbiotics (Lacticaseibacillus paracasei strain Shirota, Bifidobacterium breve strain Yakult, and galacto-oligosaccharides: LBG) helps mitigate serious adverse events such as febrile neutropenia (FN) and diarrhoea in oesophageal cancer patients receiving neoadjuvant chemotherapy (NAC). Unfortunately, LBG therapy does not benefit all patients.Hypothesis/Gap Statement. Identification of the gut microbiota species involved in adverse events during chemotherapy could help predict the onset of adverse events. Identification of the gut microbiota that influence the efficacy of LBG could also help establish a diagnostic method to identify patients who will respond to LBG before the initiation of therapy.Aim. To identify the gut microbiota involved in adverse events during NAC and that affect the efficacy of LBG therapy.Methodology. This study was ancillary to a parent randomized controlled trial in which 81 oesophageal cancer patients were recruited and administered either prophylactic antibiotics or LBG combined with enteral nutrition (LBG+EN). The study included 73 of 81 patients from whom faecal samples were collected both before and after NAC. The gut microbiota was analysed using 16S rRNA gene amplicon sequencing and compared based on the degree of NAC-associated adverse events. Furthermore, the association between the counts of identified bacteria and adverse events and the mitigation effect of LBG+EN was also analysed.Results. The abundance of Anaerostipes hadrus and Bifidobacterium pseudocatenulatum in patients with no FN or only mild diarrhoea was significantly higher (P<0.05) compared to those with FN or severe diarrhoea. Moreover, subgroup analyses of patients receiving LBG+EN showed that the faecal A. hadrus count before NAC was significantly associated with a risk of developing FN (OR, 0.11; 95 % CI, 0.01-0.60, P=0.019). The faecal A. hadrus count after NAC was positively correlated with intestinal concentrations of acetic acid (P=0.0007) and butyric acid (P=0.00005).Conclusion. Anaerostipes hadrus and B. pseudocatenulatum may be involved in the ameliorating adverse events and can thus be used to identify beforehand patients that would benefit from LBG+EN during NAC. These results also suggest that LBG+EN would be useful in the development of measures to prevent adverse events during NAC.

Long-term changes in bone mineral density in postoperative patients with esophageal cancer.

Aim: The aim of this study was to investigate long-term changes in bone mineral density (BMD) after esophagectomy, identify the risk factors for postoperative osteoporosis in patients with esophageal cancer and survival outcomes related to osteoporosis. Methods: We retrospectively evaluated BMD changes for 197 consecutive patients with thoracic esophageal cancer who were disease-free for 5 years after radical esophagectomy. Osteoporosis was diagnosed using computed tomography with an L1 attenuation threshold of ≤110 HU. Survival analysis was performed on 381 consecutive patients with 5-year follow-up after radical esophagectomy. Results: BMD decreased annually after esophagectomy. The median attenuation (HU) was 134.2 before surgery and 135.2, 127.4, 123.3, 115.2, 105.6, and 102.4 at 6 months and 1, 2, 3, 4, and 5 years after surgery, respectively. Osteoporosis was diagnosed in 25.9% patients before surgery and 23.3%, 29.4%, 40.1%, 46.7%, 54.8%, and 60.4% patients with osteoporosis were observed at 6 months and 1, 2, 3, 4, and 5 years after surgery, respectively. Postoperative BMD did not decrease in patients aged ≤54 years, those who had never been smokers, and those with no weight loss after esophagectomy. Multivariate analysis identified that age (≥65 years) at surgery and smoking history were independent risk factors for osteoporosis at 5 years after esophagectomy. Patients with preoperative osteoporosis tended to have worse prognosis in disease-free survival and overall survival than those without osteoporosis, who were more likely to die due to non-esophageal cancer. Conclusion: Esophageal cancer survivors are more likely to develop osteoporosis after esophagectomy, and preoperative osteoporosis might be associated with prognosis.

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).

Modified Collard technique is more effective than circular stapled for cervical esophagogastric anastomosis in prevention of anastomotic stricture: a propensity score-matched study.

The anastomotic technique after esophagectomy is of great interest in the prevention of anastomotic complications that adversely affect postoperative recovery. This study aimed to compare the clinical outcomes of modified Collard (MC) and circular stapled (CS) anastomoses after esophagectomy. A total of 504 consecutive patients with thoracic esophageal cancer who underwent esophagectomy and cervical esophagogastric CS or MC anastomosis from January 2013 to December 2019 were enrolled. Out of 504 patients, 134 and 370 underwent CS and MC anastomoses. The frequency of anastomotic leakage and stricture was significantly lesser in the MC group than in the CS group (3.0 vs. 10.5%, P = 0.0014 and 11.1 vs. 34.3%, P < 0.001, respectively). CS anastomosis was an independent risk factor for anastomotic stricture (odds ratio, 4.89; P < 0.001). Oral intake was significantly higher in the group without anastomotic stricture than in the group with anastomotic stricture at 2, 3, and 6 months postoperatively (P < 0.001, P = 0.013, and P < 0.001, respectively). The percentage body weight loss (%BWL) was -12.2% in the group with anastomotic stricture and -7.5% in the group without anastomotic stricture at 3 months postoperatively (P = 0.0012). Anastomotic stricture was an independent factor associated with %BWL (odds ratio, 4.86; P = 0.010). Propensity score-matched analysis, which included 88 pairs of patients, confirmed a significantly lower anastomotic stricture rate in the MC group than in the CS group (10.2 vs. 35.2%, P < 0.001). MC anastomosis is better than CS anastomosis for reducing the frequency of anastomotic stricture, which may be useful for maintaining early postoperative nutritional status.

Clinical Impact of Metastatic Lymph Node Size on Therapeutic Effect and Prognosis in Patients with Esophageal Squamous Cell Carcinoma Who Underwent Preoperative Chemotherapy Followed by Esophagectomy.

BACKGROUND: Pretreatment metastatic lymph node (LN) size has been reported to be associated with prognosis in esophageal squamous cell carcinoma (ESCC). However, its relationship with response to preoperative chemotherapy or prognosis has not been clarified. We investigated the relationship between metastatic LN size and response to preoperative treatment, and prognosis in patients with metastatic esophageal cancer who underwent surgery. PATIENTS AND METHODS: A total of 212 clinically node-positive patients who underwent preoperative chemotherapy followed by esophagectomy for ESCC were enrolled. Patients were stratified into three groups on the basis of the length of the short axis of the largest LN in pretreatment computed tomography images: < 10 mm (group A), 10-19 mm (group B), and ≥ 20 mm (group C). RESULTS: Group A had 90 patients (42%), group B had 103 patients (49%), and group C had 19 patients (9%). Group C had significantly lower percent reduction in total metastatic LN size than groups A and B (22.5% versus 35.7%, P = 0.037). Group C had significantly more metastatic LNs based on histological examination than groups A and B (10.1 versus 2.4, P < 0.001). Group C patients whose LNs responded had significantly fewer metastatic LNs than nonresponders (5.1 versus 11.9, P = 0.042). Group C had significantly poorer overall survival than groups A and B (3-year survival, 25.4% versus 67.3%, P < 0.001). However, group C patients whose LNs responded had better survival than nonresponders (3-year survival, 57.1% versus 0%, P = 0.008). CONCLUSIONS: Patients with large metastatic LNs have poor response and poor prognosis. However, if a response is obtained, long-term survival can be expected.