Influence of incomplete neoadjuvant chemotherapy on esophageal carcinoma.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Enteral Diet Enriched with ω-3 Fatty Acid Improves Oxygenation After Thoracic Esophagectomy for Cancer: A Randomized Controlled Trial.

BACKGROUND: Although the anti-inflammatory effects of immunomodulating diets (IMDs) have recently attracted attention, the efficacy of enteral feeding of such diets after radical surgery remains controversial. Thus, we conducted a new prospective, randomized controlled study to elucidate any beneficial effect of an IMD containing eicosapentaenoic acid (EPA) and γ-linolenic acid (GLA) in patients undergoing radical esophagectomy for thoracic esophageal cancer. METHODS: From November 2009 to July 2011, 87 consecutive patients were randomized to receive either an IMD enriched with EPA, GLA, and antioxidants (n = 42) or a standard isocaloric, isonitrogenous diet (control group, n = 45) after esophagectomy with radical lymphadenectomy. The primary outcome measure was changes in the oxygenation status (PaO2/FIO2 ratio), and the secondary outcome measures were body composition, inflammation-related factors, coagulation markers, cholesterol concentrations, and major clinical outcomes. RESULTS: Oxygenation was significantly better on postoperative days (PODs) 4, 6, and 8 in the IMD than control group (366.5 ± 63.3 vs. 317.3 ± 58.8, P = 0.001; 361.5 ± 52.6 vs. 314.0 ± 53.2, P < 0.001; 365.4 ± 71.2 vs. 315.2 ± 56.9, P = 0.001, respectively). Changes in the ratio of body weight on PODs 14 and 21 and lean body weight on POD 21 were significantly greater in the IMD than control group. No significant differences were observed in other measures. CONCLUSIONS: An enteral IMD enriched with EPA and GLA improved oxygenation and maintained the body composition of patients undergoing radical esophagectomy, indicating the potential efficacy of such a diet after esophagectomy.

Safety and feasibility of thoracoscopic esophagectomy after neoadjuvant chemotherapy for esophageal cancer.

PURPOSE: 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. METHODS: 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). RESULTS: 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. CONCLUSION: Based on our findings, thoracoscopic esophagectomy is safe and effective for locally advanced EC, even after NAC.

C-reactive Protein is a Useful Marker for Early Prediction of Anastomotic Leakage after Esophageal Reconstruction.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Pneumocystis Pneumonia during Adjuvant Chemotherapy for Advanced Colon Cancer - A Case Report].

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.

[Thoracoscopic radical esophagectomy for cancer treatment].

More than 15 years have passed since thoracoscopic surgery was first employed in Japan as a treatment for esophageal cancer with curative intent. Because of the proliferation of techniques that can be used to obtain an adequate operative field, such as hand assist, placing the patient in the prone position, etc., the number of approaches to thoracoscopic surgery has been increasing, contrary to expectations of standardization. The technique of mediastinal dissection has been refined with increasing knowledge of microanatomy, which can be clarified under the magnified view provided in thoracoscopic surgery. Comparable pulmonary function and survival are achieved after both thoracoscopic surgery and open-chest surgery. The accreditation board of the Japan Society for Endoscopic Surgery is now standardizing the thoracoscopic technique. To avoid surgical mistakes, thorough knowledge and adherence to the proper indications are essential.

[Selection of anticancer drug for poorly-differentiated adenocarcinoma of colorectum from the level of orotate phosphoribosyl transferase and dihydropyrimidine dehydrogenase activities in cancer tissue].

We investigated the relationship between DPD, OPRT activities and clinicopathological characteristics in 76 patients with colorectal cancer. There was no significant difference between cancer and normal tissue in DPD activity. OPRT activity was significantly higher in cancer tissue than in normal tissue. In poorly-differentiated adenocarcinoma, DPD activity was significantly higher, and OPRT activity was significantly lower than the other type of cancer. Furthermore, OPRT activity was significantly lower in patients with lymph node metastasis. These results suggested that poorly-differentiated adenocarcinoma of the colorectum shows lower efficacy with treatment by 5-fluorouracil than other types of colorectal cancer. Hence, DPD inhibitory fluorouracil, such as S-1, may have potent therapeutic efficacy for poorly-differentiated adenocarcinoma of the colorectum.

[Correlation between clinicopathological factors and enzymatic activity of orotate phosphoribosyl transferase (OPRT), dihydropyrimidine dehydrogenase (DPD) in esophageal cancer].

We investigated the relationship between orotate phosphoribosyl transferase (OPRT), dihydropyrimidine dehydrogenase (DPD) and clinicopathological characteristics in 48 patients with esophageal cancer. DPD activity resulted in no significant differences between cancer tissue and normal tissue, and no relationship with clinicopathological factors. OPRT activity was significantly increased in cancer tissue; its activity was significantly lower in patients with lymph node metastasis and lymph vessel invasion, and significantly higher in Stage I and II than in Stage III and IV. The OPRT/DPD ratio has a relation to cancer staging and survival rate. These results suggested that OPRT levels were related to the clinic pathological characteristics and survival of esophageal cancer.

[A case of SIADH developed during neoadjuvant chemotherapy using nedaplatin and 5-fluorouracil in a patient with esophageal cancer].

A 77-year-old male with thoracic esophageal cancer (cT3N3M0, Stage III) received nedaplatin at 80mg/m2 for 1 day and 5-fluorouracil at 800mg/m2 for 5 days as neoadjuvant treatment. On the fifth day of treatment, he lapsed into a coma (Japan Coma Scale 30), and his serum sodium concentration was found to be decreased to 116mEq/L. We concluded hyponatremia due to SIADH (syndrome of inappropriate secretion of antidiuretic hormone) induced by chemotherapy based on the fact that the patient had no finding of dehydration, particular history of related disorders, serum hypoosmolality accompanied by urine hyperosmolality and persistent urinary sodium excretion. We treated him with fluid restriction, sodium supplement and administration of loop diuretic. Then he regained consciousness and appropriate serum sodium level. Thereafter, hyponatremia was corrected without recurrence, and the patient underwent radical esophagectomy safely. He has been in good condition without recurrence of esophageal cancer after surgery.

Remnant gastritis should be evaluated histologically rather than endoscopically.

BACKGROUND/AIMS: Many patients who undergo distal gastrectomy develop remnant gastritis. The diagnosis of remnant gastritis is commonly established endoscopically. This report describes the correlation between endoscopic and histological findings of inflammatory changes in the remnant gastric mucosa. METHODOLOGY: Ninety-seven patients who underwent curative distal gastrectomy for gastric cancer, with radical lymphadenectomy, were studied. Endoscopy was performed 12 weeks after surgery. Patients with marked redness, erosion, or edema of the gastric remnant, as seen by endoscopy, were judged to have remnant gastritis, and were divided into group P (positive) and group N (negative). Histological remnant gastritis was evaluated with the neutrophil infiltration score based on the updated Sydney System for endoscopically taken biopsies. Cyclooxygenase (COX)-2 expression was evaluated immunohistochemically. RESULTS: There was no difference in neutrophil infiltration or COX-2 expression scores between the patients in groups P and N. There was a significant correlation between neutrophil infiltration score and COX-2 expression score (p<0.001). CONCLUSIONS: Endoscopic diagnosis of remnant gastritis was not correlated with histological findings. Histological remnant gastritis had significant correlation with COX-2 expression score, which was induced by inflammation. Therefore, proper diagnosis of remnant gastritis should be based on histological examination.

[A case of severe electrolytic disorder after adjuvant chemotherapy for esophageal cancer].

A 69-year-old female who had undergone esophagectomy for esophageal cancer was given adjuvant chemotherapy (5-FU 750 mg/body x 5 day, cisplatinum (CDDP) 100 mg/body x 1 day). An electrolytic disorder was found on day 2, and her consciousness became unclear on 5 day (respective Na, K and Cl values of 113, 2.2 and 67 mEq/L in blood). It took 59 days for infusion therapy to control electrolyte for loss in urine. As the b2-microglobulin level was high in urine and the ADH level in blood was normal, cisplatinum nephrotoxicity was thought to make this accident. Electrolytes should be checked carefully for disorder during chemotherapy.

Helicobacter pylori induces gastritis and oxidative stress after distal gastrectomy.

BACKGROUND/AIMS: Helicobacter pylori is a carcinogen for gastric cancer. There have been few reports on carcinogenesis about H. pylori infection in the gastric remnant after distal gastrectomy. The relationship between carcinogenesis and H. pylori infection was studied by means of inflammation and oxidative stress. METHODOLOGY: Ninety-seven patients who had undergone curative distal gastrectomy for gastric cancer were studied. All patients underwent endoscopic examination 3 months after surgery. The presence of H. pylori was determined using urease rapid test, hematoxylin-eosin staining, and immunohistochemical staining. Fifty-one patients were positive (group A) and 46 patients were negative (group B). The grades of remnant gastritis were scored by updated Sydney System. 8-Hydroxydeoxyguanosine (8-OHdG) as an oxidative stress marker, was analyzed immunohistochemically, and graded in 4 grades. RESULTS: Both the neutrophil infiltration score and 8-OHdG expression score was higher in group A than group B (p = 0.03 and 0.05). The correlation between the 8-OHdG expression score and the neutrophil infiltration score was significant (p = 0.02). CONCLUSIONS: As gastritis is related to oxidative stress, H. pylori infection is suspected to play an important role in carcinogenesis in the gastric remnant.

[Thoracoscopic radical esophagectomy for esophageal cancer].

Thoracoscopic esophagectomy for cancer has become common in the 10 years after the introduction of the procedure, with advances in instrumentation and techniques. Thoracoscopic surgery is associated with the advantage of preserving pulmonary function and reducing pulmonary complications by reducing chest wall injury and blood loss. Although it cannot be evaluated subjectively, understanding the microanatomy under a magnified view, education through viewing on a monitor, and the ability to reproduce the whole procedure are advantages. However, to perform lymph node dissection as efficiently as in open surgery, substantial learning of the procedure is necessary. To steepen the learning curve, sharing and disclosing knowledge and information are essential, as well as direct instruction and hands-on seminars given by skilled experts.

Laparoscopic mesorectal excision with preservation of the pelvic autonomic nerves for rectal cancer.

BACKGROUND/AIMS: 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. METHODOLOGY: 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. RESULTS: 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. CONCLUSIONS: Laparoscopic mesorectal excision with preservation of autonomic pelvic nerves for rectal cancer patients including selected advanced lower rectal cancer is favorable.

Finding Oxygen Reservoir by Using Extremely Small Test Cell Structure for Resistive Random Access Memory with Replaceable Bottom Electrode.

Although the presence of an oxygen reservoir (OR) is assumed in many models that explain resistive switching of resistive random access memory (ReRAM) with electrode/metal oxide (MO)/electrode structures, the location of OR is not clear. We have previously reported a method, which involved the use of an AFM cantilever, for preparing an extremely small ReRAM cell that has a removable bottom electrode (BE). In this study, we used this cell structure to specify the location of OR. Because an anode is often assumed to work as OR, we investigated the effect of changing anodes without changing the MO layer and the cathode on the occurrence of reset. It was found that the reset occurred independently of the catalytic ability and Gibbs free energy (ΔG) of the anode. Our proposed structure enabled to determine that the reset was caused by repairing oxygen vacancies of which a filament consists due to the migration of oxygen ions from the surrounding area when high ΔG anode metal is used, whereas by oxidizing the anode due to the migration of oxygen ions from the MO layer when low ΔG anode metal is used, suggesting the location of OR depends on ΔG of the anode.

Cytomegalovirus-associated ulceration of gastric conduit after chemoradiotherapy following esophagectomy for cancer.

A 64-year-old man underwent radical esophagectomy for cancer and simultaneous reconstruction using the gastric conduit through the posterior mediastinum. Two courses of adjuvant chemotherapy were performed. Twenty-eight months postoperatively, recurrence of the cancer was detected in the mediastinal lymph nodes, and he underwent concurrent chemoradiotherapy and boost chemotherapy. Endoscopy was then performed to investigate the cause of epigastralgia, and multiple ulcerations were found in the lesser curvature of the gastric conduit. Although a proton-pump inhibitor was orally administered, the ulceration was intractable. Re-examination of the original biopsy specimens and serological testing revealed positivity for cytomegalovirus. The ulcers began to heal after administration of foscarnet sodium. After the treatment, no signs of exacerbation associated with reinstitution of chemotherapy were observed.

Respiratory function after laparoscopic distal gastrectomy--an index of minimally invasive surgery.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.