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We have sometimes experienced technical difficulty performing thoracoscopic esophagectomy because of the position of the descending aorta or width of the mediastinal space. In this study, we retrospectively investigated predictive preoperative factors that influence the procedure of thoracoscopic esophagectomy with a focus on the position of the descending aorta and width of the mediastinal space. Ninety-five patients who underwent thoracoscopic esophagectomy for esophageal cancer by two specialists were included in this study. Thirty patients in whom both the operation time and blood loss in the thoracic region exceeded the median were categorized to the difficult group. The remaining 65 patients were categorized into the common group. During the evaluation of the position of the descending aorta, we measured the aorta–vertebra angle at the level of the left inferior pulmonary vein. During the evaluation of the width of the mediastinal space, we measured the sternum–vertebra distance at the level of the tracheal bifurcation. A forward stepwise logistic regression analysis revealed the following independent predictive factors of the technical difficulty of thoracoscopic esophagectomy: aorta–vertebra angle (≥ 30°), sternum–vertebra distance (

A 79-year-old man with underlying alcoholic liver cirrhosis presented with complaints of a fever, abdominal pain, and difficulty walking. A diagnostic work-up revealed liver atrophy and chylous ascites, and spontaneous bacterial peritonitis (SBP) was diagnosed based on the cell and neutrophil counts. The Burkholderia cepacia complex (Bcc) was detected on blood and ascitic fluid cultures. Although broad-spectrum antibiotic therapy was initiated, the infection was difficult to control, and the patient died of multiple organ failure. Bcc is often multidrug-resistant and difficult to treat. SBP caused by Bcc has been rarely reported and may have a serious course, thus necessitating caution.

Neoadjuvant chemotherapy (NAC) involving two cycles of cisplatin plus fluorouracil is recommended in Japan as a standard treatment for resectable, locally advanced esophageal squamous cell carcinoma (ESCC). We have encountered patients who were administered incomplete chemotherapy because of adverse events or the patient’s refusal of treatment. Here, we retrospectively investigated the influence on perioperative outcomes and long-term prognosis of patients with ESCC who underwent complete (two cycles) or incomplete (one cycle) NAC. We retrospectively investigated 133 patients with locally advanced ESCC of the thoracic esophagus who underwent NAC. We compared the perioperative results and prognoses of patients who underwent complete or incomplete NAC because of adverse events or the patient’s refusal of treatment. Of 133 patients, 37 patients did not receive the second cycle of NAC; the remaining 96 patients received the second cycle of NAC as scheduled. There were no significant differences in the clinical backgrounds, surgical results, or operative morbidity rates between the groups. Patients in both groups were similarly administered postoperative chemotherapy regimens. There was no significant difference in disease-free survival or overall survival. We suggest that perioperative outcomes and long-term prognosis of patients with locally advanced ESCC were not significantly influenced, even if the patients did not receive a complete cycle of NAC. When certain adverse events occur after the first cycle of NAC, we believe that it is nevertheless possible to discontinue chemotherapy.

Neoadjuvant chemotherapy (NAC) with cisplatin and fluorouracil is the recommended standard treatment for resectable locally advanced esophageal cancer (EC) in Japan. We investigated the effects of NAC on the safety and feasibility of thoracoscopic esophagectomy with total mediastinal lymphadenectomy for EC. This retrospective study analyzed data from 225 consecutive patients who underwent thoracoscopic esophagectomy with lymph node dissection between April 2007 and December 2015. Patients with clinical stage IB, IIA, IIB, IIIA, or IIIB EC, and no active concomitant malignancy were included. We compared intraoperative outcomes, and postoperative morbidity and mortality between patients who received NAC (n = 139; NAC group) and patients who did not (n = 86; non-NAC group). Preoperative laboratory data revealed that anemia, thrombopenia, and renal dysfunction were more common in the NAC group than in the non-NAC group. There were no differences between the groups in operating times, blood loss, number of dissected lymph nodes, overall complication rates, or length of postoperative hospital stay. Based on our findings, thoracoscopic esophagectomy is safe and effective for locally advanced EC, even after NAC.

We evaluated the effectiveness of neoadjuvant chemoradiotherapy (CRT) followed by esophagectomy for cT4 esophageal cancer or lymph node metastases (LNM) invading adjacent structures. We retrospectively evaluated 42 consecutive patients with thoracic esophageal cancer who underwent CRT followed by esophagectomy between 2008 and 2013. All were initially considered to be unresectable because of cT4 (n = 32) disease or LN invasion (n = 10). Radiotherapy was administered at 41.4 Gy/23 fr with concurrent chemotherapy. At completion of CRT, restaging was performed using computed tomography (CT). All cT4 tumors were downstaged, LNM invading to adjacent structures were considered to be released, and subtotal esophagectomy was performed. The median follow-up period was 42 months. The curative resection (R0) rate was 94% in cT4 group and 70% in LN invasion group. The 3-year overall survival (OS) and 3-year locoregional control (LRC) rates were 65–80% in the cT4 group and 50–67% in LN invasion group, respectively. The cT4 group showed good rates of R0, OS, and LRC. Surgical resection should be an effective option when downstaging is achieved by CRT for patients with initially inoperable thoracic esophageal cancer.

The usefulness of laparoscopic low anterior resection for middle and lower rectal cancer remains controversial.Retrospective assessment was performed on 98 patients (51 with middle and 47 with lower rectal cancer) who underwent laparoscopic rectal surgery since 1998. Total mesorectal excision was standard. Cancers were classified as middle or lower rectal based on distance from the distal tumor border to the anal verge (8 cm oror=8 cm). Laparoscopic rectal surgery was performed with five or six ports and carbon dioxide pneumoperitoneum. Rectal mobilization was usually done by electrocautery and vessels were sealed with a LigaSureV. Pelvic anatomy was accurately visualized by endoscopic magnification, so autonomic nerves could be preserved. The rectum was mobilized just above the levator muscles. Operative variables and the short- and long-term outcomes were investigated.Five open conversions were required, including three early cases related to rectal transection problems. The other two were for a large tumor and adhesions. Mean operating time was 236 min and blood loss was 147 g. Postoperative complications were 13 cases of anastomotic leakage (13.1%), 6 wound infections (6.1%), 4 cases of anastomotic bleeding (4.0%), and 3 cases of urinary retention (3.0%). Total morbidity was 32.2%, but there were no fatal complications or operative deaths. Mean postoperative period until bowel movement, oral intake, and hospital discharge was 1.6, 1.3, and 19.7 days, respectively. Twelve patients had recurrence: local in 3, lymph node in 2, lung in 5, and liver in 2. The 5-year disease-free/overall survival rates were 82.3/95.7% in stage I, 55.1/72.0% in stage II, and 59.5/80.7% in stage III.Laparoscopic low anterior resection achieves acceptable short- and long-term outcomes. It is a useful option even for advanced lower rectal cancer.

A new technique for performing laparoscopic anterior resection is described. Main differences from the standard technique are (1) pneumoperitoneum to improve exposure of the rectum, even in a narrow pelvis; (2) rectal division performed using a conventional linear stapler inserted via a 4.5 cm suprapubic incision; and (3) eversion of the rectum for tumors close to the anal verge, with transection performed under direct vision. Results in 78 patients who underwent transabdominal transection and in 7 patients requiring rectal eversion were compared retrospectively with those in 61 consecutive patients who had undergone standard laparoscopic resection. The duration of the operation and estimated blood loss were greater with rectal eversion, and more staple cartridges were used for the conventional technique; however, the incidence of complications was similar for all three groups. Five patients in the conventional group required conversion to an open procedure. The new technique should improve the safety of resection.

We report a case of pneumocystis pneumonia (PCP) during adjuvant chemotherapy for advanced sigmoid colon cancer. A 70-year-old Japanese man was referred to our hospital after complaining of bloody stools. He was diagnosed with advanced sigmoid colon cancer, T2N2aM1b, Stage IV B. After 3 cycles of mFOLFOX6 plus panitumumab as first-line chemotherapy, he received FOLFIRI plus bevacizumab as second-line chemotherapy because of progressive disease. Aprepitant and steroids were administered as antiemetic agents for a short period during each chemotherapy session. During the 2 cycle of FOLFIRI plus bevacizumab, he developed a high fever without respiratory symptoms. Chest CT revealed ground-glass opacities in both the lungs. We first treated him with antibiotics (PIPC/TAZ plus GRNX), suspecting bacterial pneumonia. However, based on the elevation of serum b -D-glucan (148 pg/mL), we diagnosed PCP and initiated SMX/TMP in addition to PIPC/TAZ. The inflammation promptly decreased, and follow-up chest CT revealed the disappearance of the ground-glass opacities. If a patient develops a fever or respiratory symptoms during a course of chemotherapy, we should consider the possibility of PCP and perform careful examinations.

Esophageal anastomotic leakage is one of the most fatal complications after esophagectomy and increases the hospitalization length. We aimed to identify a convenient clinical marker of anastomotic leakage in the early postoperative period.In total, 108 patients who underwent esophagectomy were retrospectively screened, and 96 were used to validate the overall results. All 108 patients underwent physical examinations and determination of their white blood cell count, C-reactive protein level, platelet count, fibrinogen level, fibrin degradation product level, and antithrombin III level until postoperative day 6.Anastomotic leakage occurred in 21 of the 108 patients (median detection, 8 days). The C-reactive protein level on postoperative day 3 and fibrinogen level on postoperative day 4 in the leakage group were significantly higher than those in the nonleakage group. Receiver operating characteristic curves for detection of anastomotic leakage were constructed; the cutoff value of C-reactive protein on postoperative day 3 was 8.62 mg/dL, and that of fibrinogen on postoperative day 4 was 712 mg/dL. Anastomotic leakage occurred in 23 of the 96 patients in the validation group. There was a significant difference between the leakage and nonleakage groups when the C-reactive protein threshold on postoperative day 3 was set at 8.62 mg/dL. However, there was no difference between the groups when the fibrinogen threshold on postoperative day 4 was set at 712 mg/dL.The C-reactive protein level on postoperative day 3 is a valuable predictor of anastomotic leakage after esophagectomy and might allow for earlier management of this complication.

Self-expandable metallic stent (EMS) placement has been the first choice for dysphagia because of the certainty over its safety, low invasiveness, and immediate efficacy. However, there still remain some problems in relation to the EMS placement site and anticancer therapies before and after EMS placement. Methods: Consecutive 78 patients in whom EMS was placed due to the unresectable malignant stricture in the esophagus or cardia from July 1995 to August 2003 in our department were studied. Results: Gastroesophageal reflux was found in 5 of 8 patients after placement of conventional EMS for the stricture in the gastroesophageal junction. Meanwhile, acid and bile reflux into the esophagus were not detected by pH and bilirubin monitoring, respectively, in 6 patients after placement of the EMS with an anti-reflux mechanism for the stricture in the gastroesophageal junction. The median survival period of all patients after EMS placement was 123 days. The median survival period of 7 patients with radiotherapy only after EMS placement was 138 days and that of 17 patients with radiotherapy before EMS placement was 60 days, which was shorter than that of the former (p

Background: The efficacy of thoracoscopic radical esophagectomy for cancer of the thoracic esophagus and the learning curve required have yet to be clearly established. Methods: Eighty treatment-naive patients with esophageal cancer without contiguous spread underwent esophageal mobilization and extensive mediastinal lymphadenectomy through a 5-cm minithoracotomy and four trocar ports. The outcomes in the first 34 patients (group 1) and the last 46 patients (group 2) were compared. Results: There were no differences in background or clinicopathologic factors between the two groups. The duration of the thoracoscopic procedure and blood loss were less (p

We examined the course of a primary hepatic neuroendocrine carcinoma (PHNEC) patient and analyzed the postoperative outcome of all reported PHNEC cases.A literature search for PHNEC cases was performed using PubMed. All reported cases and our present patient were analyzed in this study. Survival analysis was performed using the Kaplan-Meier method. Risk factors for the recurrence of PHNEC following hepatic resection were investigated.A total of 43 patients were analyzed in this study. The 3-, 5-, and 7-year overall survival rates were 55%, 48%, and 48%, respectively. The 3-, 5-, and 7-year overall survival rates in surgery patients were 78% each, and 25%, 17%, and 17%, respectively in nonsurgery patients. Lymph node metastasis posed a significant risk factor for postoperative recurrence.Hepatic surgery is an appropriate therapeutic treatment for PHNEC without distant metastasis nor lymph node metastasis. Adjuvant chemotherapy might be necessary for PHNEC patients with lymph node metastases.

The aim of this study was to evaluate the clinical outcomes and prognostic factors of thoracoscopic esophagectomy with two-field lymph node dissection for lower thoracic esophageal cancer.From January 2003 to December 2011, 84 patients with lower thoracic esophageal cancer underwent thoracoscopic esophagectomy with two-field lymph node dissection. Clinicopathological information, postoperative complications, mortality, type of recurrent diseases and factors predictive of survival were analyzed.Postoperative complications were diagnosed in 37 patients and the mortality was 1.2%. Lymph node metastases were found in 43 patients (51.2%). The 5-year survival rate of all patients was 60.5%. Pathological T factor, lymph node metastasis, pathological staging, and venous invasion were independent prognostic factors. Among the patients with lymph node metastasis, the survival rate of those with upper mediastinal and/or celiac area involvement was significantly worse than that of those without involvement of these areas.Thoracoscopic esophagectomy with two-field lymph node dissection is a safe and appropriate surgical intervention for patients with lower thoracic esophageal cancer without complication of lymph node metastases to the upper mediastinum and/or celiac area.

Various types of granulocyte colony-stimulating factor (G-CSF)-producing malignant tumors have been reported. However, a G-CSF-producing colorectal cancer is rare. We present a case of G-CSF-producing ascending colon cancer. An 81-year-old man was referred to our hospital with right lower abdominal pain. A colon fiberscopy revealed an ascending colon tumor, and histological examination revealed tubular adenocarcinoma. He was admitted due to worsening abdominal pain. Although laboratory data showed an elevated white blood cell (WBC) count of 17000/mm3 with 77.8% neutrophils, elevated C-reaction protein (CRP) was insignificant (1.06 mg/dL), and he was afebrile. Because computed tomography indicated that the tumor penetrated into surrounding tissue, a semi-urgent ileocecal resection was performed. An abscess was not located. The tumor was staged as T3N2aM0 and as stage IIB according to the TNM classification. Microscopically, significant neutrophil infiltration between cancer cells was observed, suggesting the presence of a G-CSF-producing tumor. Immunohistochemical staining using a G-CSF antibody revealed cytoplasmic staining in cancer cells. The serum concentration of G-CSF upon admission was 334 pg/mL. After surgical resection, the WBC count decreased to within a normal range. These findings confirmed the diagnosis of G-CSF-producing ascending colon cancer. The prognosis of G-CSF-producing tumors is considered to be poor. Early diagnosis and surgical treatment are needed for patients with G-CSF-producing tumors, and continuous careful follow-up is required.

Background Anastomosis performed during esophagectomy for esophageal cancer is usually involves hand-sewn or circular stapled methods. However, these techniques have been reported to be associated with a high frequency of anastomotic complications, including leakage and benign stenosis. Here a novel triangulating stapling technique for esophagogastrostomy after esophagectomy for esophageal cancer and its retrospective investigation are described. Methods Forty-eight patients were underwent esophagectomy for esophageal cancer from January 2006 to December 2009 by the same surgeon using the triangulating stapling technique. The short-term outcomes were evaluated retrospectively. This end-to-end anastomosis used three linear staplers in an everted fashion. Results Patients comprised 36 men and 12 women with a mean age of 59.4 years. Anastomotic leakage occurred in 4 patients (8.3 %), while anastomotic stenosis was observed in 6 (12.5 %). The average number of endoscopic pneumatic dilatations in patients with anastomotic stenosis was 2.4. The median (range) duration of hospital stay was 40.8 (19–154) days. Conclusions Our modified triangulating stapling technique for esophagogastrostomy may be a feasible alternative, resulting in a lower frequency of postoperative anastomotic complications.

Aneurysm of the middle colic artery is very uncommon. In this report, we describe a case of a ruptured aneurysm of the middle colic artery caused by segmental arterial mediolysis and its successful management by surgical resection. A 60-year-old Japanese man was admitted to our institution for the treatment of a ruptured aneurysm of the branch of the superior mesenteric artery suspected by computed tomography. Angiography revealed multiple wide and narrow mural irregularities and some aneurysms in the middle colic artery without extravasation. Transcatheter arterial embolization could not be accomplished because of difficulty in catheterization. Since radiological findings of the patient indicated worsening of the aneurysm, surgical resection was performed. Histopathological findings of the resected specimen were consistent with those of segmental arterial mediolysis. In cases where curative embolization cannot be accomplished, surgical resection is required. However, in a non-ruptured aneurysm, healing occurs gradually. Therefore, if the vital parameters of the patient are stable, conservative observation can be recommended.

We reported herein four resected cases with basaloid carcinoma of the esophagus and measured the activity of 5-FU related enzymes (TS, DPD, OPRT) in cancer tissue. These activities compared with those in squamous cell carcinoma. Only one case was diagnosed as basaloid carcinoma by preoperative biopsy specimen at endoscopic examination. The esophagectomy was performed thoracoscopically in all cases, and the abdominal procedure was done with the laparoscopic approach in two cases. Anastomotic leakage occurred in one case. No case had lymph node metastasis. On the other hand, a lymphatic invasion was detected in one case, and venous invasion in two, respectively. Two cases had mediastinal lymph node recurrence. DPD activity and OPRT activity showed no difference between squamous cell carcinoma and basaloid carcinoma. On the other hand, the TS activity was significantly higher in basaloid carcinoma. From the standpoint of 5-FU-related enzyme activities, basaloid carcinoma possibly has more resistance to 5-FU than squamous cell carcinoma.

Purpose: We retrospectively investigated the impact of prior abdominal surgery on the outcome of laparoscopic colorectal surgery. Patients: Among 607 colorectal cancer patients who underwent laparoscopic surgery, 192 patients had previously undergone abdominal surgery (S group) and 415 had not (non-S group). Results: The percentage of female patients was higher in the S group than in the non-S group. The incidence of conversion to open surgery was higher in the S group (5.2%, 10/192) than in the non-S group (2.6%, 11/415), but the difference was not significant (p = 0.108). Although the mean operating time and estimated blood loss were similar in the two groups, right and transverse colectomy after prior gastrectomy and ipsilateral colectomy after prior colectomy took longer and were associated with greater blood loss. The morbidity rates of the two groups were similar (S group: 15.6%, 30/192; non-S group: 14.5%, 60/415). There were 5 intraoperative small-bowel injuries or postoperative small-bowel perforations in the S group, especially in the patients with prior gastrointestinal-tract surgery. Conclusion: Our findings suggest that there is no reason to avoid laparoscopic procedures in most patients with prior abdominal surgery despite a higher conversion rate, but caution is warranted in patients who have undergone major gastrointestinal-tract surgery.

The role of laparoscopic surgery in the management of stage IV colorectal cancer remains uncertain.Sixty-five patients with stage IV disease from among 578 colorectal cancer patients who underwent laparoscopic surgery since 2001 were compared with 513 patients who had stage 0-III disease. The criteria for excluding stage IV patients from laparoscopic surgery were huge tumors, low rectal cancer, massive ascites due to peritoneal seeding, bowel perforation and/or obstruction, and poor general condition and/or cachexia. Data were analyzed by chi-square test or Student's t-test, with P0.05 being considered significant.The two groups of patients had similar demographic features. The open conversion rate was 4.6% (3/65 patients) in the stage IV group and 2.7% (14/513 patients) in the stage 0-III group, and the difference between the groups was not significant. In the stage IV group, depth of tumor invasion and tumor diameter were both significantly greater than in the stage 0-III group. However, operating time and blood loss were similar in the two groups (stage IV: 189.0 min and 95.0 g; stage 0-III: 182.5 min and 60.0 g), although blood loss was significantly greater in the stage IV group when patients undergoing rectal surgery were compared. The incidence of postoperative complications and the postoperative course of the two groups were similar.Despite their larger and more invasive tumors, the short-term outcome of laparoscopic surgery in patients with stage IV colorectal cancer was similar to that for stage 0-III patients. This result indicates that laparoscopic surgery can be successfully performed in selected stage IV colorectal cancer patients.

Laparoscopic mesorectal excision with preservation of the autonomic pelvic nerves for rectal cancer including selected advanced lower rectal cancer is now challenging. The aims of the study were to assess the surgical results and short-term outcomes of this procedure prospectively.Seventy-four of 281 rectal cancer patients, since the introduction of laparoscopic colorectal surgery in our hospital, have undergone laparoscopic rectal surgery. The location of the tumor distributed in upper rectum; 33, middle; 22, and lower 19. The mesorectal excision with preservation of the autonomic pelvic nerves was performed for all the patients. The laparoscopic mesorectal excision was performed under 8 to 10 cmH2O CO2 pneumoperitoneum and lymph node dissection was performed along the feeding artery depend on individuals. Ipsilateral lateral lymph node dissection was added for 5 cases of advanced lower rectal cancer.Open conversion occurred in 4 cases, 2 of those were due to locally advanced tumors and 2 technical difficulties in transaction of the distal rectum. There were 15 postoperative complications, 7 anastomotic leakage (10.6%), 3 transient urinary retention (4.1%), 4 wound infection (5.3%), and 1 small bowel obstruction (1.4%). No mortality was recorded in this series. Time of operation was 203 +/- 54 min in mesorectal excision cases and 270 +/- 42 min mesorectal excision with lateral lymph node dissection cases. Blood loss was 92 +/- 90g and 276 +/- 66 g respectively. The hospital length-of-stay was 11.7 days in average.Laparoscopic mesorectal excision with preservation of autonomic pelvic nerves for rectal cancer patients including selected advanced lower rectal cancer is favorable.

As the techniques of laparoscopic surgery have improved, various institutions have performed laparoscopic gastrectomies with regional lymph node dissection, as well as open surgery. Although alleviation of postoperative pain and prompt recovery have been reported in the literature, objective indexes of the minimal invasiveness of laparoscopic procedures are as yet very few.We performed distal gastrectomy with regional lymph node dissection for gastric cancer patients using three kinds of procedures, namely, open gastrectomy, hand-assisted laparoscopic surgery (HALS), and totally laparoscopic gastrectomy. Ablation of the stomach, lymph node dissection, and reconstruction of the digestive tract were all carried out intracorporeally with or without HALS in the laparoscopic procedures. The ordinary respiratory function test was performed pre- and postoperatively for 50 patients operated on by each procedure, and the reduced percentages of the measured values were calculated.Postoperative respiratory function was consistently excellent, with minimal loss of vital capacity and forced expiratory volume per second in the totally laparoscopic group compared to HALS or open cases.Although it may be a complicated technique, totally laparoscopic distal gastrectomy is considered a minimally invasive procedure for gastric cancer from the viewpoint of postoperative respiratory function.

TS-1 is often used as first-line chemotherapy for treatment of advanced or recurrent gastric cancer, but there is no definite therapeutic policy for patients for whom TS-1 is not effective, or to whom it cannot be administered. We have treated 6 patients with low-dose weekly paclitaxel therapy as second-line chemotherapy after initial treatment with TS-1. These patients consisted of 3 males and 3 females with a mean age of 56 years. Four patients had recurrent gastric cancer and two had unresectable advanced gastric cancer. Paclitaxel was administered in doses of 80 or 100 mg weekly. Adverse events more severe than grade 3 were not observed, but there were 2 cases of leukopenia (grade 1) and 2 cases of decreased hemoglobin (grade 2). Mean survival time after the administration of paclitaxel was 139 days. Five patients died of their cancer, and one is still alive 382 days after the paclitaxel administration. The one-year survival rate after administration was 16.7%. Low-dose weekly paclitaxel therapy is therefore safe and effective for patients with advanced and recurrent gastric cancer who previously received TS-1 therapy.

A case of recurrent gastric cancer with metastases to the skin and lung was treated successfully with low-dose paclitaxel after oral TS-1 administration. The patient was a 73-year-old man who underwent total gastrectomy for gastric cancer on April 3, 2000. Two years and four months after the operation, an increasing CA19-9 concentration and metastases to the skin and both lungs were observed. Oral TS-1 was given, but had to be stopped because of diarrhea. The metastatic lesions of the skin were resected, and low-dose paclitaxel (100 mg) was given once a week for 6 weeks. Five months later, the metastatic lesions of the right and left lung had decreased in size by 62% and 100%, respectively. CA19-9 fell to below the cut-off value 2 months after starting therapy. A decrease in the hemoglobin level of grade 1 was observed. Low-dose paclitaxel for recurrent gastric cancer after TS-1 therapy causes few side effects and may well be effective.

Irinotecan hydrochloride (CPT-11) is a potent anti-cancer drug with suppressive effects against gastric and colorectal cancers. However, no evaluation of CPT-11 for esophageal squamous cell carcinoma has been performed in vivo. In this study, we examined the tumor suppressive effects of CPT-11 on N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis. One hundred and fourteen rats were divided into six groups. Rats in groups 1-5 were treated with subcutaneous injection of NMBA at a dose of 0.5 mg/kg 3 times per week for 5 weeks. Rats in group 6 served as a control. Rats in groups 2 and 3 were treated with intragastric (i.g.) administration of CPT-11 at doses of 20 and 40 mg/kg, respectively, once a week simultaneously with NMBA-initiation up to the end of the experiment. Rats in groups 4 and 5 were treated with i.g. administration of CPT-11 at doses of 20 and 40 mg/kg, respectively, once a week after the NMBA-initiation period up to the end of the experiment. The incidence of papilloma and hyperplasia in the esophagus showed no difference between NMBA-treated groups. However, the multiplicity of hyperplasia was significantly reduced in all CPT-11 administration groups. Immunohistochemically, expression of proliferating cell nuclear antigen (PCNA) was decreased on carcinogen-exposed squamous epithelium and preneoplastic lesions, although no significant differences were detected in the expression of single-strand DNA (ssDNA) and p53. These data suggest that CPT-11 has suppressive effects for esophageal tumors in the early step of the multistep process of carcinogenesis through antiproliferative mechanism.

This is a report of a case with esophageal cancer in which pathological CR was obtained by neoadjvant chemoradiotherapy using a low-dose of nedaplatin (CDGP)/5-FU. The patient was a male aged 76. A protuberant lesion diagnosed as esophageal cancer was found in the middle thoracic esophagus by esophagography. Since another lesion in the upper thoracic esophagus was revealed by endoscopy, metastasis to the cervical lymph nodes was diagnosed by ultrasonography, and preoperative chemoradiotherapy combining a low dose of CDGP/5-FU with radiotherapy was performed. As side effects of this treatment, grade 2 stomatitis and granulocytopenia were observed. The main lesion of the esophagus was found to have significantly diminished through endoscopy after completion of the treatment, and with no malignant cells obtained by biopsy. No cervical lymph nodes were found. It was diagnosed as partial response (PR) through imaging diagnosis. Radical resection of esophageal cancer under right thoracotomy and laparotomy was performed. Operative findings were Ch x R-T3N0M0 Stage II R0 D2 Cur A. Pathological examination of resected specimens revealed no viable cancer cells in the esophagus or metastasis to the dissected lymph nodes. Neoadjuvant chemoradiotherapy using a low-dose of CDGP/5-FU is an effective treatment for esophageal cancer.

Helicobacter pylori infection is known to induce gastritis, oxidative stress, and cyclooxygenase (COX)-2 expression in the gastric mucosa. However, the effect of H. pylori infection on remnant gastritis has not been studied. We investigated whether the severity of remnant gastritis and COX-2 expression were affected by H. pylori infection after distal gastrectomy.The study included 97 patients with gastric cancer who underwent curative distal gastrectomy with lymphadenectomy in our department between May 1999 and April 2001. All patients underwent endoscopic examination 2 weeks before and 12 weeks after surgery. The presence of H. pylori infection was determined by urease activity, hematoxylin-eosin staining, and immunochemical staining. Histologic remnant gastritis was graded based on the degree of neutrophil infiltration using the updated Sydney System. COX-2 expression was estimated immunohistochemically.Both the degree of neutrophil infiltration and the level of COX-2 expression were significantly higher in patients with than without H. pylori (p0.05). There was a significant correlation between the degree of neutrophil infiltration and the degree of COX-2 expression (p0.001).H. pylori eradication may become a treatment for preventing both remnant gastritis as well as remnant gastric carcinoma after distal gastrectomy.

Patients who undergo distal gastrectomy often develop duodenogastric reflux and preoperative H. pylori infection is eradicated spontaneously after distal gastrectomy in some patients. However, whether a causal relationship exists has not yet been studied. This report examines the correlation between H. pylori eradication and the amount of duodenogastric reflux following distal gastrectomy.Among 72 consecutive patients who underwent curative distal gastrectomy with radical lymphadenectomy for gastric cancer, 37 patients had H. pylori infection preoperatively and were included in this study. The period of bile reflux (percent time) into the gastric remnant was measured with the Bilitec 2000 under standardized conditions on the 14th day after the surgery. Endoscopic examination was performed to determine the presence of H. pylori infection on week 12 after surgery.The percent time was higher in patients whose H. pylori infection had been eradicated after distal gastrectomy (58.1+/-9.2%) than in patients who had H. pylori infection after distal gastrectomy (33.8+/-5.7%).Duodenogastric reflux correlates with spontaneous eradication of H. pylori infection following distal gastrectomy.

5-FU is the most widely used anticancer drug for digestive system cancers, and it has been recently reported that the effect of 5-FU varies with the amount of enzymes that are involved in the drug metabolism in the cancer tissue. In this report, we measured DPD and OPRT activities in the normal mucosa and colorectal cancer tissues and compared them with clinicopathological factors to examine the choice of chemotherapy for colorectal cancers. Forty-six patients with colorectal carcinoma (28 colon and 18 rectal cancers), which were resected in our department from 1999 to March 2003, were examined. There was no significant difference in the DPD activities between the normal and cancer tissues, whereas OPRT showed significantly higher activity in the cancer tissues. Although we did not find a relation between the DPD activity and clinicopathological factors, the OPRT activity showed a significant difference between gender and classification of tumor, and mucinous adenocarcinoma showed significantly lower OPRT activity than differentiated adenocarcinoma. The DPD activity of mucinous adenocarcinoma is related to catabolism of 5-FU is equal to that of adenocarcinoma, however, the OPRT activity is related to a main pathway of 5-FU phosphorylation is significantly lower. Thus, mucinous adenocarcinoma of the colon was more resistant to 5-FU than the differentiated adenocarcinoma. Therefore, for chemotherapy of mucinous adenocarcinoma, anticancer agents other than 5-FU should be selected.

We present an unusual case of a benign esophagobronchial fistula caused by radiotherapy to treat esophageal carcinoma which was closed successfully. A 62-year-old man with superficial squamous cell carcinoma of the esophagus underwent radiotherapy, including 60 Gy externally and 10 Gy intraluminally from January to March 1995. Esophagography revealed a fistula between the esophagus and left main stem bronchus on January 14, 1996. No residual cancer existed. Neither stenting with a silicone tube nor with a covered flexible metallic stent occluded the fistula. Thoracic esophagectomy, closure of the esophagobronchial fistula using a 2-cm nubbin of esophageal wall, surrounding the orifice of the fistula and antesternal gastric pull-through reconstruction with mediastinal lymphadenectomy were performed. The postoperative course was uneventful and there is no evidence of recurrence of the fistula or the cancer 5 years postoperatively. Radiotherapy may cause esophagobronchial fistula even in cases of superficial esophageal cancer. Bypass surgery should be considered because stenting is not effective for benign fistula without stricture.

A 55-year-old man was referred to us after transverse colostomy for intestinal obstruction caused by descending colon cancer with peritoneal dissemination. The colon lesion was palpated as a well-defined hard mass in the left lower abdomen and the disseminated lesion as a hard mass with an unclear border in the right lower abdomen. CEA level was 917 ng/ml at admission. Left hemicolectomy was performed for tumor reduction and TS-1 of 120 mg/day was started 6 days after surgery (4 weeks administration followed by a 2-week rest period). Administration discontinued due to nausea 4 weeks after commencement of the therapy, and restarted as a 2-week administration followed by a 2-week rest period. There has been no adverse reaction since then. Twenty-seven weeks after surgery, CEA level was reduced to 47 ng/ml and peritoneal dissemination was found to have disappeared upon physical examination and computed tomograph. TS-1 is expected to be an effective agent for the treatment of colon cancer with peritoneal dissemination.

We report a case of esophageal cancer infiltrating the left main bronchus in which radical esophagectomy with clear surgical margins could be performed after preoperative radiochemotherapy. The patient was a 57-year-old man, who was found to have esophageal squamous cell carcinoma of the middle thoracic esophagus during a work-up of dysphagia. Bronchoscopy revealed an elevated region protruding into the lumen of the left main bronchus. After radiochemotherapy (liniac irradiation + low-dose FP therapy), the esophageal and bronchial lesion became smaller. The case was evaluated as a clinically complete response. Bronchoscopic ultrasonography showed a clear boundary between the membranous portion of the trachea and the esophageal wall. Based on these findings, the lesion was considered resectable and radical surgery, including 3-field lymph node dissection, was performed. The resected esophageal specimen had residual cancer cells in the muscularis propria covered with normal mucosa. However, the patient is currently healthy with no evidence of disease. The indication for surgical resection in cases of esophageal cancer with contiguous spread, and a good response to preoperative radiochemotherapy, is controversial. It is necessary to verify the effectiveness of surgical resection, as a secondary treatment, by accumulating data on cases such as the present one.

A case of esophageal tuberculosis presenting with an appearance similar to that of esophageal cancer is reported. The patient was an 82-year-old man with progressive dysphagia. Barium swallow and esophagoscopy revealed an elevated lesion with deep ulceration in the middle thoracic esophagus. Esophageal carcinoma, in particular, an undermining type of undifferentiated carcinoma, was suspected fluoroscopically and endoscopically. Histological examination of biopsy specimens revealed no malignancy, but there were epithelioid granulomas and a few Langhans' type multinucleated giant cells. Endoscopic ultrasonography clearly demonstrated an extramural lesion with calcification and direct infiltration of enlarged subcarinal lymph nodes into the esophageal wall. Ultrasonographic and histological findings indicated the possibility of esophageal tuberculosis. Although no bacteriological evidence was obtained, a therapeutic trial for tuberculosis, using antituberculous drugs, was started. After 2 weeks, the enlarged subcarinal lymph nodes were markedly reduced in size. The patient's symptoms improved gradually and had disappeared 8 weeks after he started treatment, when tubercle bacilli were isolated from sputum. A connection between the esophageal wall and its adjacent structures was clearly demonstrated by endoscopic ultrasonography. For patients with findings indicative of esophageal tuberculosis on endoscopic ultrasonography, a therapeutic trial for tuberculosis should be considered, even if polymerase chain reaction assay or culture is negative.

Improved understanding of how esophageal cancer behaves following curative resection, including knowledge of other causes of death, is essential for informed decision making. The medical records of 246 consecutive patients with squamous cell carcinoma of the thoracic esophagus who had undergone esophagectomy and lymphadenectomy of the neck, chest, and abdomen that was deemed macroscopically curative, were reviewed. Patients who had had other malignancies or anticancer treatment were excluded. Median follow-up period was 1289 days (minimum, 730 days). The initial patterns of recurrence were classified as intramediastinal, hematogenous, or lymphatic. Forty-two patients died of a cause other than recurrence. The in-hospital death rate was 3.6%, and 19 patients died of pulmonary disease. Sixteen patients developed a second primary, most of which were in the upper aerodigestive tract; five of those patients died. Ninety-eight patients developed recurrence. Depth of invasion and number of nodal metastases predicted recurrence. The pattern of recurrence was intra-mediastinal, lymphatic, and hematogenous in 11, 21, and 67 patients, respectively. The patients with lymphatic recurrence survived longer than the patients with either of the other types of recurrences. Eighty-three percent of recurrences presented within 24 months. The time-to-recurrence correlated with survival after recurrence. The disease recurred earlier in patients with advanced stage than unadvanced disease at the time of esophagectomy. The time-to-recurrence, and anticancer therapy after the recurrence related to the survival. Meticulous care must be taken to detect hematogenous recurrence as early as possible so that adjuvant therapy may be started. Maintaining a good performance status permits the use of aggressive therapy should there be a recurrence. Pulmonary physiotherapy and treatment of metachronous primary tumors may improve overall survival.

The role of reflux of duodenal contents in gastroesophageal reflux in Japanese patients, which may be different from that in Western patients, was studied. Methods: Intraesophageal pH and the bilirubin concentration were monitored, using the Bilitec 2000, in 43 patients with reflux symptoms and 10 normal volunteers. The percentage of the time that spectrophotometric absorbence was 0.15 or more and pH was less than 4.0 was defined as the holding times (HTs) of bilirubin and acid, respectively. Severity of esophagitis was classified using the Savary-Miller (S-M) classification. Results: Esophagitis was present in 37 patients; 5, 10, 13, and 9 patients had S-M grades 1, 2, 3, and 4, respectively. Both HTs in the volunteers were less than 5%. Bilirubin HT was more than 5% in 3 of the 6 patients without esophagitis, but the acid HT was less than 5% in these 6 patients. Acid HT was less than 5% in 4, 2, 2, and 2 patients with S-M grades 1, 2, 3, and 4, respectively. Bilirubin HT was less than 5% in 1 patient with S-M grade 2 esophagitis. Bilirubin HT in patients with S-M grades 3 and 4 esophagitis (50.9 ± 5.8%) was higher than that in grades 1 and 2 (14.9 ± 2.9%) (P < 0.0001), but this was not so for acid HT. In 32 patients, bilirubin HT exceeded acid HT. Bilirubin HT did not correlate with acid HT. Conclusions: Duodenogastroesophageal reflux occurred independently of and exceeded acid reflux. The amount of duodenogastroesophageal reflux correlated with the severity of esophagitis.

The survival of gastric cancer patients with peritoneal dissemination is dismal and surgical intervention is rarely indicated. The usefulness of TS-1, a novel oral anticancer drug, composed of tegafur, gimestat and otastat potassium at a molar ratio of 1:0.4:1, and the role of surgical intervention for this condition was studied. Among gastric cancer patients with peritoneal dissemination, 18 treated during September 1999 to March 2001, and 16 before March 1999, were classified into the TS-1 group and control group, respectively, and survival was compared. TS-1 was administered orally twice daily, at a dose of 80 mg/m2/day, for 28 days followed by 14 days without treatment. This cycle was repeated. There was no difference in clinicopathologic factors, including surgical intervention, between the two groups. Eleven patients of the control group had chemotherapy using fluoropyrimidine. Grade 3-4 adverse reactions caused by TS-1 occurred in 1 patient. Survival was better in the TS-1 group than control group (p=0.0008), with median survival of 257 vs. 118 days. The median discharged period of patients of the TS-1 group with a performance status 0-2 on the Zubor scale was 211 days. TS-1 was effective to prolong the survival of gastric cancer patients with peritoneal dissemination. In this series of cases, surgical intervention to establish the route of oral administration was essential for this treatment.