Effect of Four Main Gastrectomy Procedures for Proximal Gastric Cancer on Patient Quality of Life: A Nationwide Multi-Institutional Study.

PURPOSE: This study aimed to examine the effects of 4 main types of gastrectomy for proximal gastric cancer on postoperative symptoms, living status, and quality of life (QOL) using the Postgastrectomy Syndrome Assessment Scale-45 (PGSAS-45). MATERIALS AND METHODS: We surveyed 1,685 patients with upper one-third gastric cancer who underwent total gastrectomy (TG; n=1,020), proximal gastrectomy (PG; n=518), TG with jejunal pouch reconstruction (TGJP; n=93), or small remnant distal gastrectomy (SRDG; n=54). The 19 main outcome measures (MOMs) of the PGSAS-45 were compared using the analysis of means (ANOM), and the general QOL score was calculated for each gastrectomy type. RESULTS: Patients who underwent TG experienced the lowest postoperative QOL. ANOM showed that 10 MOMs were worse in patients with TG. Four MOMs improved in patients with PG, while 1 worsened. One MOM was improved in patients with TGJP versus 8 MOMs in patients with SRDG. The general QOL scores were as follows: SRDG (+39 points), TGJP (+6 points), PG (+3 points), and TG (-1 point). CONCLUSIONS: The TG group experienced the greatest decline in postoperative QOL. SRDG and PG, which preserve part of the stomach without compromising curability, and TGJP, which is used when TG is required, enhance the postoperative QOL of patients with proximal gastric cancer. When selecting the optimal gastrectomy method, it is essential to understand the characteristics of each and actively incorporate guidance to improve postoperative QOL.

Clinical practice guideline for the treatment of malignant ascites: section summary in Clinical Practice Guideline for peritoneal dissemination (2021).

Patients with peritoneal dissemination (PD) caused by abdominal malignancies are often associated with massive ascites, which shows extremely dismal prognosis because of the discontinuation of systemic chemotherapy mostly due to poor performance status. Many treatment methods, such as simple drainage, peritoneovenous shunting (PVS) and cell-free and concentrated reinfusion therapy (CART), have been used for symptom relief. However, the clinical efficacies of these methods have not been fully investigated yet. Recently, we developed the Clinical Practice Guideline for PD caused by various malignancies according to "Minds Clinical Practice Guideline Development Guide 2017". In this guideline, we systematically reviewed information on clinical diagnosis and treatments for PD using PubMed databases (2000 - 2020), and clarified the degree of recommendation for clinical questions (CQ). The evidence level was divided into groups by study design and quality. The literature level and a body of evidence were evaluated in reference to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Based on the results of systematic review, the strength of the recommendations was evaluated at a consensus meeting of the Guideline Committee. This is the English synopsis of the part of treatment of malignant ascites in Clinical Practice Guideline for PD, 2021 in Japanese. The guidelines summarize the general aspect of the treatment of malignant ascites and statements with recommendation strengths, evidence levels, agreement rates and future perspective for four raised clinical questions.

Roux-en-Y Plus Distal Jejunal Pouch After Total Gastrectomy: A Prospective Study.

BACKGROUND/AIM: We previously described the safety of distal jejunal pouch with Roux-en-Y reconstruction after total gastrectomy. The present prospective study evaluated its clinical benefit. PATIENTS AND METHODS: Forty-five patients with gastric cancer were preoperatively assigned to groups who underwent Roux-en-Y reconstruction with jejunal pouch (PRY) (n=23) or without pouch (RY) (n=22). Age, sex, grade of lymph node dissection, splenectomy and mode of laparotomy were analyzed, and body mass index (BMI), volume of food intake at one sitting and blood chemistry (total protein, hemoglobin, iron and cholesterol) were periodically assessed in both groups. RESULTS: Post-surgical mortality and severe morbidity did not occur. Three and four patients in the PRY and RY groups, respectively, died of gastric cancer recurrence during the study. BMI at six months after surgery was significantly higher in the PRY than in the RY group (p<0.05). The percentage of food intake at one year after the procedure was significantly higher in the PRY than in the RY group (p<0.05). CONCLUSION: The distal jejunal pouch ameliorated postoperative weight loss and increased food intake. A distal jejunal pouch with PRY reconstruction may confer significant clinical advantages after total gastrectomy. The long-term clinical benefit of this procedure should be evaluated.

Evaluation of laparoscopic cholecystectomy using indocyanine green cholangiography including cholecystitis: A retrospective study.

Intraoperative cholangiography involving the excretion of fluorescent indocyanine green (ICG) into the bile is used to determine biliary anatomy in laparoscopic cholecystectomy (LC). This study aimed to evaluate the features of intraoperative ICG cholangiography, in LC with cholecystitis, and compared the delineation of the cystic duct (CD) between ICG cholangiography and magnetic resonance cholangiopancreatography (MRCP).Participants comprised 65 patients undergoing LC using ICG cholangiography.Fifty-eight patients (89.2%) were diagnosed with gallbladder stones and 32 (49.2%) with acute cholecystitis. ICG cholangiography identified CD in 54 patients (83.1%) and did not identify CD in 11 patients (16.9%). The mean value of the fluorescence intensity in the identified CD group by ICG cholangiography was 87.6 ±â€Š31.5 arbitrary unit and that in the not identified CD group by ICG cholangiography was 24.4 ±â€Š10.1 arbitrary unit (P < .001). Compared with the patients in the identified CD group, those in the not identified CD group had higher incidence of acute cholecystitis (P < .001), and higher conversion rates (P = .003). A correlation between the delineation of CD by ICG cholangiography and MRCP was analyzed, and it revealed a correlation between each other (P = .002)Inflammation had harmful effects with regard to the passing of CD. If we can identify CD or common bile duct with ICG cholangiography, we may be able to perform LC with confidence, even in the presence of severe inflammation.

A phase II, randomized study of aprepitant in the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapies in colorectal cancer patients.

The present study aimed to study the efficacy of aprepitant in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy (MEC) for colorectal cancer (CRC), and comprised a multicenter, phase II, open-label, randomized, parallel comparative study conducted as part of the Kagoshima aprepitant study for colon cancer in Japan. Patients with advanced or recurrent CRC were treated with standard MEC regimens (FOLFOX, XELOX or FOLFIRI) and received either standard chemotherapy [5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) + dexamethasone] or aprepitant regimen chemotherapy (5-HT3 RA + reduced-dose dexamethasone + aprepitant). The primary endpoint of the present study was the proportion of patients who achieved a complete response (CR) during the overall, acute, and delayed phases of the first planned chemotherapy cycle. Secondary endpoints were complete protection, the proportions of patients without emetic episodes or nausea, patients with no more than moderate nausea during the overall, acute and delayed phases, and the time to treatment failure. The CR rates in the overall, acute and delayed phases were similar in the aprepitant and the standard-regimen groups. Additionally, there were no significant differences in secondary endpoints between the two groups. In summary, aprepitant in combination with 5-HT3 RA and reduced-dose corticosteroids was well tolerated and effective in preventing CINV associated with moderately emetogenic antitumor agents in Japanese patients with CRC.

Diagnostic performance of ¹8F-fluorothymidine PET/CT for primary colorectal cancer and its lymph node metastasis: comparison with ¹8F-fluorodeoxyglucose PET/CT.

PURPOSE: To examine the diagnostic performance of (18)F-fluorothymidine (FLT) PET/CT in primary and metastatic lymph node colorectal cancer foci in comparison with (18)F-fluorodeoxyglucose (FDG) PET/CT. METHODS: The study population comprised 28 patients with 30 newly diagnosed colorectal cancers who underwent surgical resection of the primary lesion and regional lymph nodes after both FLT and FDG PET/CT. The associations between SUVmax levels and pathological factors were evaluated using the Mann-Whitney U or Kruskal-Wallis test. Differences in diagnostic indexes for detecting nodal metastasis between the two tracers were estimated using the McNemar exact or χ(2) test. RESULTS: All 30 primary cancers (43.0 ± 20.0 mm, range 14 - 85 mm) were visualized by both tracers, but none of the FLT SUVmax values exceeded the FDG SUVmax values in any of the primary cancers (6.6 ± 2.4 vs. 13.6 ± 5.8, p < 0.001). The sensitivity, specificity and accuracy for detecting nodal metastasis were 41% (15/37), 98.8% (493/499) and 94.8% (508/536) for FDG PET/CT, and 32% (12/37), 98.8% (493/499) and 94.2% (505/536) for FLT PET/CT, respectively. The sensitivity (p = 0.45), specificity (p = 0.68) and accuracy (p = 0.58) were not different between the tracers. Nodal uptake of FLT and FDG was discordant in 7 (19%) of 37 metastatic nodes. There were ten concordant true-positive nodes of which six showed higher FDG SUVmax and four showed higher FLT SUVmax, but the difference between FDG and FLT SUVmax was not significant (5.56 ± 3.55 and 3.62 ± 1.45, respectively; p = 0.22). CONCLUSION: FLT has the same potential as FDG in PET/CT for the diagnosis of primary and nodal foci of colorectal cancer despite significantly lower FLT uptake in primary foci.

High FDG and low FLT uptake in a thyroid papillary carcinoma incidentally discovered by FDG PET/CT.

We report a 58-year-old man whose incidentally discovered papillary thyroid carcinoma in the left lobe showed high FDG and low FLT uptake on PET/CT. The SUVmax was 19.7 for FDG and 3.0 for FLT. The Ki-67 labeling index of the tumor was 1.9%. Thus, the low FLT uptake might be attributed to the low proliferative activity of this cancer.

Roux-en-Y reconstruction with stapled distal jejunal pouch after total gastrectomy.

Roux-en-Y reconstruction after total gastrectomy is a simple and safe procedure; however, it eliminates the gastric reservoir function and markedly changes the postoperative digestive physiology. The patients therefore suffer from insufficient food intake and malabsorption. It has been reported that jejunal pouch reconstruction increases food intake and improves the nutritional status. We established a novel Roux-en-Y reconstruction with stapled distal jejunal pouch after total gastrectomy. A jejunal pouch, 8 cm in size, was attached at the jejunojejunostomy. We performed this novel reconstruction for 20 gastric cancer patients after total gastrectomy with lymph node dissection as a feasible study. One year after operation, the average percentage weight was maintained in more than 90 per cent and 17 (85%) of these patients were in the normal range of the body mass index. This procedure may improve postoperative malnutrition after total gastrectomy according to our feasible study. A multicenter randomized trial of this approach comparing with Roux-en-Y reconstruction without a pouch is ongoing.

Midkine is highly expressed in neuroblastoma tissues.

PURPOSE: Neuroblastoma (NBL) is a tumor from neural crest cells, and is the most frequent solid tumor in children. Midkine (MK) is a pleiotropin analogon, which is frequently expressed in neuronal and epithelial tumors and is a marker for a poor clinical outcome. The aims of this study were to assess MK expression in NBL and investigate the correlation with clinical outcome. METHODS: Fifty-six specimens of NBL were stained for MK on a tissue microarray by immunohistochemistry (IHC). Fresh frozen tumor tissues were used for RNA isolation, and RT-PCR analysis for MK-mRNA expression was performed. Survival data, risk factors and disease stages were correlated with MK status assessed by IHC and RT-PCR analysis. RESULTS: MK-mRNA expression was found in the majority of the tumor tissues (75%), whereas MK protein could be detected only in 46% of the NBL by IHC. No correlation of MK status with survival, risk factors or disease stage was observed. CONCLUSION: A majority of NBL express MK-mRNA, whereas not all MK mRNA positive tumors showed also a positive MK IHC staining. The high expression of MK-mRNA expression might present a promising target for new adenovirus-based gene therapeutic approaches for the treatment of NBL.

A multicenter phase II study of biweekly paclitaxel and S-1 combination chemotherapy for unresectable or recurrent gastric cancer.

PURPOSE: This Phase II study assessed the activity and safety of biweekly paclitaxel and oral S-1 as treatment for unresectable and recurrent gastric cancer. The maximum tolerated dose for this regimen had been established previously in a Phase I study performed in Japanese patients. PATIENTS AND METHODS: Chemotherapy was performed using two anticancer agents, S-1 and paclitaxel. Oral S-1 (80 mg/m(2)) was administered twice a day after meals for two consecutive weeks from Day 1 to 14, followed by a 2 week recovery period; paclitaxel (120 mg/m(2)) was administered intravenously, biweekly, on Days 1 and 15. The patient received cycles of this regimen every 4 weeks (q 28-day cycles). The primary end point was the response rate according to the Response Evaluation Criteria in Solid Tumors. RESULTS: A total of 39 patients (median age, 65 years) were enrolled; 13 other patients were screened, but found to be ineligible. All patients had unresectable and recurrent gastric cancer. The most common treatment-related Grade 3/4 adverse events were neutropenia (37.5%), appetite loss, diarrhea, decreased sodium (each 5%), and anemia, increased alanine aminotransferase, general fatigue, and dizziness (each 2.5%). Almost all the patients experienced alopecia. Intent-to-treat analysis showed a response rate of 43.6%. With a median follow-up of 14 months (range 8-21 months), median survival was 256 days and the median time to progression was 4 months. CONCLUSION: A combination regimen of biweekly paclitaxel and oral S-1 was well tolerated and showed promising activity against unresectable and recurrent gastric cancer.

Thy-1 as a potential novel diagnostic marker for gastrointestinal stromal tumors.

PURPOSE: Only few immunohistochemical markers besides c-kit exist for gastrointestinal stromal tumors (GISTs). Thy-1, a cell-surface glycoprotein, is a marker for several types of stem cells and particularly for neuronal precursor cells. The aim of this study was to determine Thy-1 expression in GISTs. MATERIALS AND METHODS: Fifty-seven surgically resected and paraffin-embedded GIST samples were analyzed by immunohistochemistry with peroxidase method for Thy-1 molecule. RESULTS: Thy-1 was detected in the majority of 57 GIST samples (54 out of 57 patients, 95%). All samples were c-kit positive and 90% were CD34 positive. All three Thy-1 negative samples were CD34 positive, had a low proliferative index (Ki-67

Successful treatment of advanced gastric cancer by surgical resection following combination chemotherapy with oral S-1 and biweekly paclitaxel.

We report on the successful treatment of advanced gastric cancer by surgical resection following neoadjuvant chemotherapy. A 67-year-old man was referred to our hospital with a diagnosis of pancreatic cancer. Meticulous examination, however, revealed the presence of gastric cancer with ascites and large lymph node metastasis adjacent to the pancreas. We selected combination chemotherapy with oral S-1 and biweekly paclitaxel. After two courses, both the primary tumor and metastatic lymph nodes were greatly reduced, and the ascites had disappeared. Using laparoscopy, there was no evidence of peritoneal metastases, and the cytological examination was negative. The patient underwent distal gastrectomy with D2 lymph node dissection. Histological examination revealed that the cancer cells were still present in part, but no lymph node metastases were found. The tumor was pathologically diagnosed as pT2, pN0, P0, M0, CY0, and p-stage II. The patient is healthy over 4 years after surgery without recurrence.

Midkine as a prognostic marker for gastrointestinal stromal tumors.

PURPOSE: Midkine (MK), a heparin-binding growth factor, has an important role in cancer progression. The outcome of patients with gastrointestinal stromal tumors (GISTs) is correlated with tumor size and mitotic count. The aim of this study was to determine MK expression in GISTs. METHODS: Midkine was detected in 31 (55%) of 57 surgically resected GISTs by immunohistochemistry with a rabbit antibody against MK and peroxidase method. RESULTS: A significant worse outcome of MK-positive patients was found (P < 0.05; log rank test). Multivariate Cox regression analysis showed an independent prognostic impact (relative risk for overall survival 3.64; P < 0.05). Interestingly, MK expression was significantly associated with mitotic rate (P < 0.05; Chi-squared test), but not with tumor size (P = 0.97). CONCLUSIONS: Taken together, MK is a prognostic marker for GIST patients. MK might also be a useful peripheral tumor marker since it can be detected in peripheral serum. Future studies should involve higher GIST patient numbers including tumor and serum samples for detection of MK.

The successfully curative treatment of advanced gastric adenocarcinoma with multiple liver metastases and paraaortic lymph node metastases by salvage operation following the biweekly paclitaxel and S-1 combination chemotherapy: a case report.

We report the case of 67-year-old man who was given a diagnosis of advanced gastric adenocarcinoma. Complete response of multiple liver and paraaortic lymph node metastases occurred in this patient after combination chemotherapy with systemic injection of paclitaxel and oral administration of novel dihydropyrimidine- dehydrogenase- inhibitory fluoropyrimidine (S-1). Following 7 courses of the biweekly paclitaxel and S-1 combination chemotherapy, the patient underwent total gastrectomy with D3 extended lymph node dissection. According to the operative findings, the tumor was curatively removed along with the liver metastases and paraaortic lymph node metastases. Biopsy of the liver was performed and the pathological diagnosis indicated no gastric adenocarcinoma cells. The pathological report showed that the lymph node metastases had completely disappeared with single exception and minute cancerous lesions were identified in the gastric mucosa and submucosa. Therefore, the histological efficacy was evaluated as Grade 2. For postoperative chemotherapy, oral S-1 administration only was chosen. However, 6 months later, biweekly paclitaxel and S-1 combination chemotherapy was administered in sequence as a second adjuvant chemotherapy because the serum level of the tumor marker was elevated. The patient is fine and has not shown any recurrence at other sites 37 months after surgery. Salvage surgery following paclitaxel and S-1 chemotherapy may be feasible for patients with advanced gastric cancer and complete regression of distant metastases. Biweekly paclitaxel and S-1 combination chemotherapy has been used safely and its administration may be continued for a long time in an outpatient clinic setting for the treatment of advanced gastric cancer.

[A case of advanced rectal carcinoma, preoperative chemo-radiation therapy leading to histological complete response].

A 49-year-old male was admitted to Sendai Saiseikai Hospital with a complaint of upper abdominal pain. Perforative rectal cancer was diagnosed, and an emergency laparotomy was done. Transient colostomy and drainage for peritonitis were performed. Preoperatively rectal cancer was assessed to invade the sacral bone and prostate. A total of 50 Gy radiation therapy with low dose CDDP+5-FU chemotherapy was conducted for five weeks. Remarkable shrinkage of the tumor was found, and elective surgery for curative intent was done on April 2000. The tumor seemed to invade the adjacent tissues such as prostate and urine bladder, so extensive resection of the urine bladder and sacral bone was done in addition to abdominal perineal resection. Pathological exploration showed complete regression of the tumor and no tumor invasion to the prostate and sacral bone. He is well without tumor relapse. Once complete regression of the rectal cancer by chemo-radiation therapy has been achieved, relapse of the tumor was reported to be rare. Preoperative chemo-radiation therapy is an effective tool to control the advanced rectal cancer.

[Combination chemotherapy study of biweekly paclitaxel and S-1 administration in patients with advanced gastric cancer].

In the present article, we report the results of phase I/II combination chemotherapy study of biweekly paclitaxel and S-1 administration in patients with advanced gastric cancer. In the phase I study, we could determine the recommended dose for the phase II study with paclitaxel and S-1 to be 120 mg/m2 and 80 mg/m2, respectively. The side effect was not so severe. The overall response was 53%. In conclusion, biweekly paclitaxel and S-1 administration can be safely combined for the treatment of advanced gastric cancer. This combined therapy represents a novel and active treatment regimen with low toxicity and can be defined as safe and effective. Now we are analyzing the result of the phase II study.

A phase I combination chemotherapy study of biweekly paclitaxel and S-1 administration in patients with advanced gastric cancer.

The aim of the current study was to determine the maximum tolerated dose (MTD) and the dose limiting toxicity (DLT) of a combination of paclitaxel and S-1 in patients with advanced gastric cancer. Fifteen patients were enrolled. The dose for S-1 was set at 80 mg/m2/day (days 1-14), while the dose for paclitaxel increased by 10 mg/m2 for every three patients, with a starting dose of 100 mg/m2 and was given biweekly on day 1 and 15. There was no severe toxicity (grade 4) recorded in patients receiving up to 120 mg/m2 of paclitaxel. Leukopenia/neutrophilia with grade 1 to 3 occurred in six patients up to level 3. At 130 mg/m2 of paclitaxel, grade 4 leukocytopenia and neutropenia events and grade 3 diarrhea developed in one out of three patients. One patient in another group of three patients that were enrolled at level 3, developed grade 4 granulocytopenia with fever (a body temperature higher than 38 degrees C) and grade 3 leukocytopenia. Eight patients, out of a total of 15, showed a partial response, resulting in an objective response rate of 53%. Five patients received gastrectomy. Median survival time was 428 days and the 1 year survival rate was 53%. Biweekly paclitaxel/S-1 combination chemotherapy could be safely used for the treatment of advanced gastric cancer. The recommended doses for a phase II study with paclitaxel and S-1 are 120 mg/m2 and 80 mg/m2, respectively.

[Radiation therapy leading to complete response of residual lymph node metastasis in advanced gastric cancer].

A 74-year-old male was admitted to Sendai Saiseikai Hospital with a complaint of upper abdominal pain. Gastrointestinal fibroscopy showed type 2 gastric cancer in the lower third of the stomach,and distal gastrectomy and D 2 lymph node dissection were performed. Metastatic lymph node 8 a had severely infiltrated the pancreas, and pancreatoduodenectomy was required to complete the curative surgery. However, because of preoperative complications of interstitial pneumonia, metastatic node 8 a remained untreated. Postoperatively, radiation therapy (38 Gy plus a boost of 18 Gy) for residual lymph node metastasis was performed over a one-month period. The metastatic node underwent complete regression following radiation therapy, and the patient was discharged without any adverse effects. He received TS-1 medication as postoperative adjuvant therapy. Four years have passed since the complete regression of the lymph node,and the patient has shown no signs of relapse. Therefore, our case suggests that postoperative radiation therapy can be a useful tool for treatment of residual lymph node metastasis in gastric cancer.

Bone marrow micrometastasis detected by RT-PCR in esophageal squamous cell carcinoma.

The clinical implications of bone marrow micrometastases (BMM) detected by RT-PCR in esophageal squamous cell carcinoma (ESCC) have not been elucidated. We evaluated the relation between the presence of BMM, both before and after surgery, and clinicopathologic findings in patients with ESCC. Bone marrow samples from 48 patients with ESCC were obtained from the iliac crest before and after surgery. After total RNA was extracted from each bone marrow sample, carcinoembryonic antigen (CEA)-specific RT-PCR was performed. BMM was detected by RT-PCR in 10 of the 48 patients. Four patients each had positive signals only before or only after surgery and 2 patients had positive signals both before and after surgery. There were no significant differences in clinicopathologic factors, including neoadjuvant therapy, between patients with BMM and without BMM. To date, the rates of recurrent disease in patients with BMM and without BMM are 80% (8/10) and 50% (19/38), respectively, a difference which is not significant. The 4-year survival rates of patients with BMM and without BMM are 10.0% and 47.3%, respectively. Recurrence and survival rates were poorer in patients with RT-PCR positivity, although the differences were not significant. A larger study is required to clarify the clinical impact of BMM.

Clinical impact of micrometastasis of the lymph node in gastric cancer.

Micrometastasis in regional lymph nodes has been observed immunohistochemically, but the biological and clinical roles of minute nodal invasion of carcinoma in gastric cancer remain unclear. We used the anti-cytokeratin (AE1/AE3) antibody to immunohistochemically detect nodal micrometastatic lesions that could not be identified by routine pathological examination. A total of 4203 lymph nodes were examined in 180 gastric cancer patients. Lymph node metastasis was found in 36 of the 180 patients by routine pathological evaluation. Immunohistochemically micrometastasis was detected in the lymph nodes of 19 node-negative patients. Micrometastasis was not detected in any of the mucosal gastric cancer patients who underwent lymph node dissection. Gastric cancer patients with more than six metastatic lymph nodes all had nodal micrometastasis. Patients with micrometastasis had a significantly poorer survival rate than those without micrometastasis (P < 0.05). Based on the present results the presence of lymph node micrometastasis may provide a more accurate indication for surgical outcome in gastric cancer patients at the same clinical stage.