Conversion surgery for gastric cancer patients: A review

Gastric cancer (GC) is the third most common cancer-related cause of death worldwide. In locally advanced tumors, neoadjuvant chemotherapy has recently been introduced in most international Western guidelines. For metastatic and unresectable disease, there is still debate regarding correct management and the role of surgery. The standard approach for stage IV GC is palliative chemotherapy. Over the last decade, an increasing number of M1 patients who responded to palliative regimens of induction chemotherapy have been subsequently undergone surgery with curative intent. The objective of the present review is to analyze the literature regarding this approach, known as “conversion surgery”, which has become one of the most commonly adopted therapeutic options. It is defined as a treatment aiming at an R0 resection after chemotherapy in initially unresectable tumors. The 13 retrospective studies analyzed, with a total of 411 patients treated with conversion therapy, clearly show that even if standardization of unresectable and metastatic criteria, post-chemotherapy resectability evaluation and timing of surgery has not yet been established, an R0 surgery after induction chemotherapy with partial or complete response seems to offer superior survival results than chemotherapy alone. Additional larger sample-size randomized control trials are needed to identify subgroups of well-stratified patients who could benefit from this multimodal approach.     

晚期胃癌的姑息性放疗价值研究回顾

适合做放疗的胃癌患者,根据病史及疗前影像、病理学检查等,可分为以下3种:(1)局部晚期不可手术切除或复发后胃癌;(2)初诊即有远处转移的Ⅳ期胃癌;(3)严重临床症状的胃癌。通过33篇有关胃癌姑息放疗文献(近5年8篇,近10年13篇)的阅读与理解,阐述姑息性放疗对晚期胃癌患者的作用和价值。     

T_1期和T_2期胃癌的外科治疗(兼评早期胃癌的临床意义)

目的　通过分析Ｔ１ 期和Ｔ２ 期胃癌的疗效,评价外科治疗对早期胃癌的临床意义。方法　对１３２ 例接受根治性手术的Ｔ１ 、Ｔ２ 期胃癌患者的预后进行回顾性分析。结果　Ｔ１ 和Ｔ２ 期患者的肿瘤平均大小、术中淋巴结转移率、术后复发率以及术后生存率差异均有显著性,进一步分析发现,术中已有淋巴结转移的Ｔ１ 期患者的术后生存率,明显低于术中无淋巴结转移的同期患者;而术中无转移的Ｔ２ 期患者的术后生存率,与Ｔ１ 期患者的生存率相似。结论　Ｔ１ 期（ 早期）胃癌,如已有淋巴结转移,亦应施行Ｄ２ 手术;而属进展期的Ｔ２ Ｎ０ 期胃癌,由于手术治疗预后好,在考虑是否采用术后辅助治疗时可按早期胃癌对待     

High prevalence of peritoneal metastasis in gastric cancer presenting gastric outlet obstruction: A new candidate for consecutive diagnostic staging laparoscopy and laparoscopic gastrojejunostomy

IntroductionGastric cancer presenting gastric outlet obstruction (GC-GOO) is associated with two problems to be considered in its treatment: peritoneal metastasis and an inability to intake food. Because peritoneal metastasis is difficult to identify in standard examinations, laparoscopic gastrojejunostomy (LGJ), which consecutively follows diagnostic staging laparoscopy (DSL), may be a minimally invasive solution to these diagnostic and therapeutic problems. However, whether GC-GOO is a new candidate for DSL has been not evaluated.Materials and methodsGC-GOO patients who were surgically treated at our department between 2005 and 2014 were recruited. Patient backgrounds, preoperative and surgical findings for distant metastasis, and surgical curability were retrospectively evaluated. To predict peritoneal metastasis, the sensitivity, specificity, and positive and negative predictive values of preoperative factors were calculated. The survival outcomes were also evaluated according to surgical curability and non-curative factors.ResultsA total of 237 patients with GC-GOO were included in this study. Among them, 167 patients had no distant metastasis identified preoperatively. Seventy-one of 167 patients underwent curative surgery while 75 (44.9%) had peritoneal metastasis including positive lavage cytology. Ascites and large type 3 or type 4 tumors indicated high specificity (86.9% and 76.1%, respectively) and the involvement of gastric angle presented high sensitivity (90.7%) for peritoneal metastasis. The overall survival of patients with incurable surgery was worse than that of patients with curative surgery, regardless of their incurable factors.ConclusionGC-GOO is a new candidate for DSL. DSL followed by LGJ may be proposed, utilizing preoperative predictive factors for peritoneal metastasis.     

Staging laparoscopy in patients scheduled for pancreaticoduodenectomy minimizes hospitalization in the remaining life time when metastatic carcinoma is found

Objective

To compare the burden of total hospitalization as a ratio of survival of staging laparoscopy versus prophylactic bypass surgery in patients with unresectable periampullary adenocarcinoma.

Background

Periampullary adenocarcinoma is an aggressive cancer with up to 35% of the patients at surgery found to be unresectable. Palliative prophylactic surgical bypass versus endoscopic stenting has been addressed by randomized controlled trials, but none reported on the burden of hospitalization.

Methods

From a prospective database all patients with periampullary adenocarcinomas with a preoperative patent biliary stent and absent gastric outlet obstruction, but found unresectable during surgery, were analysed. They underwent a staging laparoscopy only versus prophylactic palliative bypass surgery. In-hospital days of the initial admission as well as all consecutive admission days during the remaining life span were compared both in absolute numbers and as relative impact.

Results

The inclusion criteria were met by 205 patients. Of these 131 patients underwent a staging laparoscopy detecting metastases in 21 patients. In 184 laparotomies 54 patients underwent prophylactic palliative bypass surgery for unresectable disease. Median total in-hospital-stay in the Laparoscopy Group was 3 days versus 11 days in the Palliative Bypass Group (p = 0.0003). Patients with metastatic disease found during laparoscopy stayed 3.5% of the remaining life time in hospital vs. 10.0% (p = 0.029) in patients with metastatic disease who underwent bypass surgery.

Conclusions

Staging laparoscopy and early discharge in patients with metastatic peri-ampullary carcinoma resulted in reduced hospitalization, both in absolute number of days and as a rate of survival time.     

Experience of surgical morbidity after palliative surgery in patients with gastric carcinoma

Background Indications for palliative surgery in gastric carcinoma (GC) are controversial. Our aim was to describe the results of palliative surgery in GC in terms of operative morbidity and survival. Methods We conducted a retrospective cohort study of patients with GC, who were divided into three groups: resection with microscopic residual disease (R1), palliative resection with macroscopic residual disease (R2), and gastrojejunostomy. Comparisons were tested with analysis of variance (ANOVA) or χ² test, and the Kaplan-Meier method was used for survival analysis. Results One hundred and thirty-two patients were included in the study: 21 had R1, 71 had R2, and 40 had gastrojejunostomy. Surgical morbidity was recorded in 4 patients (19%), 23 patients (32.4%), and 1 patient (2.5%) in each of the three groups, respectively (P = 0.001). Operative mortality occurred in 6 patients (8.5%) from the R2 group and in 1 (2.5%) patient from the gastrojejunostomy group (P = 0.406). Median survivals of the R1, R2, and gastrojejunostomy groups were 22.8 months (95% confidence interval [CI], 16.4–29.3), 12.4 (95% CI, 9.01–15.8) months, and 6.4 months (95% CI, 0–14.6), respectively (P = 0.078) Conclusion R1 resections and gastrojejunostomy were associated with low surgical morbidity and mortality, unlike R2 resection; in this group, surgical morbidity and mortality was high. Therefore, the benefit of palliative resection in the presence of extensive residual disease should be balanced against the risk of surgical morbidity.     

Modified controlling nutritional status score: A refined prognostic indicator depending on the stage of gastric cancer

BackgroundThe role of controlling nutritional status (CONUT) score in predicting cancer survival remains uncertain. This study aimed to investigate the predictive value of the CONUT score and to develop a more appropriate scoring system beyond CONUT for gastric cancer.MethodsWe retrospectively reviewed 1307 patients who underwent curative gastrectomy between 2009 and 2015. The CONUT and three modified scores with modified lipid components (L-CONUT: albumin/total lymphocyte count [TLC]/low density lipoprotein, H-CONUT: albumin/TLC/high density lipoprotein, and T-CONUT: albumin/TLC/triglyceride) were calculated. The predictive value of each scoring system on long-term survival was assessed.ResultsThe values of the four nutritional scores were categorized into four groups (normal, light, moderate, and severe). The CONUT (P < 0.001), L-CONUT (P < 0.001), H-CONUT (P < 0.001), and T-CONUT (P < 0.001) scores showed significant differences in overall survival in between groups. Survival analysis according to the pathological stage showed that advanced age, Eastern Cooperative Oncology Group performance status, male sex, and moderate H-CONUT score (HR, 3.970; 95% CI, 1.826–8.633; P = 0.001) were independent worse prognostic factors for overall survival in the stage I group. In the stage II group, light CONUT score (HR, 2.230; 95% CI, 1.067–4.664; P = 0.033) and moderate CONUT score (HR, 5.077; 95% CI, 1.647–15.650; P = 0.005) were significantly associated with poor prognosis. In the stage III group, no scoring system showed significant results.ConclusionIn advanced gastric cancer (beyond stage II), the prognostic impact of the nutritional scoring system was uncertain. However, the H-CONUT score is a promising indicator of prognosis in stage I, and the CONUT score is useful for predicting long-term survival in stage II gastric cancer.     

早期胃癌的诊治体会（附61例报告）

目的 提高早期胃癌检出率,改善胃癌预后,并探讨其临床特点。方法 回顾分析６１例早期胃癌的临床表现,病灶大小,部位,分型,检测方法,治疗及预后。结果 ６１例患者平均年龄近５０岁,占同期胃癌手术病例的５．７％,Ｘ线双重造影检出率为５８．７％,胃镜肉眼检出率为４４．３％,胃镜下活检检出率可提高为９５．１％,病理诊断凹陷型者（Ⅱｃ,Ⅲ）居多,平坦型者（Ⅱｂ）易误诊,术后５９例均无瘤生存,其中生存１－４年者     

Usefulness of polysaccharide K (PSK) as postoperative adjuvant immunotherapy in patients with stage IV gastric cancer

Background. We investigated retrospectively the usefulness of polysaccharide K (PSK) administration for prolonging survival after noncurative resection in patients with stage IV gastric cancer who underwent surgery at our department. Methods. 357 patients with gastric cancer evaluated as stage IV according to thegeneral rules for gastric cancer study, 11th edn (1985) of the Japanese Research Society for Gastric Cancer, who were expected to succumb to surgical death or postoperative death within 2 months were studied. The patients were divided into two groups: total PSK dosage greater than or less than 180g. Survival rates were calculated for each group. Results. In these stage-IV gastric cancer patients, the 5-year and 10-year survival rates in the PSK group were both 13.9%. In the non-PSK group, the rates were 8.7% and 7.0%, respectively. The survival rates were significantly higher in the PSK group (p = 0.0001). The survival rate was also calculated with respect to the staging factors. Patients in the PSK group who had H0, P0, se or milder and n3 or n4 showed a significantly higher survival rate than those with these staging factors in the non-PSK group (p = 0.010). Conclusion. PSK administration prolonged survival in stage-IV gastric cancer patients, the effect being marked in patients with severe lymph node metastasis. We suggest that be administered as adjuvant therapy in stage-IV gastric cancer patients with severe lymph node metastasis (n3, n4).     

Volume-outcome relation in palliative systemic treatment of metastatic oesophagogastric cancer

IntroductionPalliative systemic therapy has been shown to improve survival in metastatic oesophagogastric cancer. Administration of palliative systemic therapy in metastatic oesophagogastric cancer varies between hospitals. We aimed to explore the association between the annual hospital volume of oesophagogastric cancer patients and survival.MethodsPatients diagnosed in the Netherlands between 2005 and 2013 with metastatic oesophagogastric cancer were identified in the Netherlands Cancer Registry. Patients were attributed according to three definitions of high volume: (1) high-volume incidence centre, (2) high-volume treatment centre and (3) high-volume surgical centre. Independent predictors for administration of palliative chemotherapy were evaluated by means of multivariable logistic regression analysis, and multivariable Cox proportional hazard regression analysis was performed to assess the impact of high-volume centres on survival.ResultsOur data set comprised 4078 patients with metastatic oesophageal cancer, and 5425 patients with metastatic gastric cancer, with a median overall survival of 20 weeks (95% confidence interval [CI] 19–21 weeks) and 16 weeks (95% CI 15–17 weeks), respectively. Patients with oesophageal cancer treated in a high-volume surgical centre (adjusted hazard ratio [HR] 0.80, 95% CI 0.70–0.91) and a high-volume treatment centre (adjusted HR 0.88, 95% CI 0.78–0.99) exhibited a decreased risk of death. For gastric cancer, patients treated in a high-volume surgical centre (adjusted HR 0.83, 95% CI 0.74–0.92) had a superior outcome.ConclusionImproved survival in patients undergoing palliative systemic therapy for oesophagogastric cancer was associated with treatment in high-volume treatment and surgical centres. Further research should be implemented to explore which specific factors of high-volume centres are associated with improved outcomes.     

Combined modality treatment of gastric cancer

In a series of 46 patients with localized gastric cancer treated at Massachusetts General Hospital, problems with excessive acute or chronic toxicity due to combination treatment with irradiation (XRT) and chemotherapy (CT) were not seen. Forty of the 46 received combined treatment with 2 regimens: 1) Irradiation plus concomitant 3 days of 5-FU followed by maintenance 5-FU or combined drugs--26 patients; 2) In the other 14 patients, the sequence of irradiation and chemotherapy was altered. A single course of combined drug chemotherapy was given prior to irradiation and 5-6 additional courses were administered after completion of XRT (CT-XRT-CT). The drug combination was initially 5-FU-BCNU but this was changed to FAM (5-FU, Adriamycin, Mitomycin C). Irradiation was delivered to tightly contoured portals using shaped blocks to spare as much small bowel, kidney and marrow as possible while giving 4500-5200 rad in 25 to 29 fractions over 5 to 6 weeks. In this series, there were no cases of septicemia or any deaths related to treatment. A 3 year survival rate of about 20% was achieved for the total group of patients and 43% in the group with resection but at high risk for later failure. Our inability to improve these numbers is undoubtedly a result of dose limitations with external beam irradiation combined with a systemic failure problem. When irradiation is combined with surgical resection of all or a majority of tumor, both survival and local control appear to be better than in the unresected patient group. Only 4 of 29 patients (14%) with curative resection, or resection but residual disease, had later evidence of failure within the irradiation field as opposed to 6 of 9 or 66% in the group with unresectable disease.     

塞来昔布联合化疗治疗晚期胃癌的疗效分析

目的 观察选择性环氧合酶2（cylooxygenase-2,COX-2）抑制剂塞来昔布联合多西他赛和替吉奥方案治疗晚期胃癌的临床疗效和不良反应。方法 将50例晚期胃癌患者随机分为两组,试验组25例采用塞来昔布联合多西他赛和替吉奥方案化疗,对照组25例给予单纯多西他赛和替吉奥方案化疗,2个周期治疗后评估两组近期疗效和不良反应,同时观察生存情况。结果 完成2个周期治疗后,试验组有效率为60%,疾病控制率为96%,对照组分别为52%和92%,两组比较差异均无统计学意义（P＞0.05）;两组治疗后不良反应发生率差异亦无统计学意义（P＞0.05）;试验组生活质量改善率高于对照组,差异有统计学意义（60% vs 32%,P＜0.05）。试验组和对照组中位无疾病进展生存期差异亦有统计学意义（7.6个月vs 6.3个月,P＜0.05）;但中位总生存期差异无统计学意义（13.6个月vs 12.2个月,P＞0.05）。结论 塞来昔布联合多西他赛和替吉奥治疗晚期胃癌与单用化疗疗效相当,无疾病进展生存期延长,可改善生活质量且不增加不良反应。     

PSCA基因rs2976392位点多态性与胃癌发病的关系

目的研究PSCA基因（pmstatestemcellantigen,PSCA）rs2976392位点多态性与胃癌发病的关系。方法收集155例汉族胃癌患者与210名健康人群的外周血液样本,提取基因组DNA,采用DNA直接测序法进行PSCA基因rs2976392位点的基因分型。结果PSCA基因rs2976392位点3种基因型GG型、GA型和AA型在胃癌组中的频率分别为43．23％、41．94％和14．84％,在对照组中分别为50．95％、41．43％和7．62％。与GG型比较,携带GA型和AA型基因型者胃癌发生的风险性增加,OR分别为1．19（95％CI=0．77～1．86）（P〉0．05）和2．30（95％CI=1．13～4．66）（P〈0．05）。结论PSCA基因rs2976392位点AA基因型与中国汉族人群的胃癌发病有关。     

Expression profiles of gastric cancer molecular subtypes in remnant tumors

BACKGROUNDRemnant gastric cancer (RGC) is a carcinoma arising in the stomach remnant after previous gastric resection. It is frequently reported as a tumor with a poor prognosis and distinct biological features from primary gastric cancer (PGC). However, as it is less frequent, its profile regarding the current molecular classifications of gastric cancer has not been evaluated.AIMTo evaluate a cohort of RGC according to molecular subtypes of GC using a panel of immunohistochemistry and in situ hybridization to determine whether the expression profile is different between PGC and RGC.METHODSConsecutive RGC patients who underwent gastrectomy between 2009 and 2019 were assessed using seven GC panels: Epstein-Barr virus in situ hybridization, immunohistochemistry for mismatch repair proteins (MutL homolog 1, MutS homolog 2, MutS homolog 6, and PMS1 homolog 2), p53 protein, and E-cadherin expression. Clinicopathological characteristics and survival of these patients were compared to 284 PGC patients.RESULTSA total of 40 RGC patients were enrolled in this study. Compared to PGC, older age (P < 0.001), male (P < 0.001), lower body mass index (P = 0.010), and lower hemoglobin level (P < 0.001) were associated with RGC patients. No difference was observed regarding Lauren’s type and pathologic Tumor Node Metastasis stage between the groups. Regarding the profiles evaluated, EBV-positive tumors were higher in RGC compared to PGC (P = 0.039). The frequency of microsatellite instability, aberrant p53 immunostaining, and loss of E-cadherin expression were similar between RGC and PGC. Higher rates of simultaneous alterations in two or more profiles were observed in RGC compared to PGC (P < 0.001). According to the molecular classification, the subtypes were defined as EBV in nine (22.5%) cases, microsatellite instability in nine (22.5%) cases, genomically stable in one (2.5%) case, and chromosomal instability in 21 (52.5%) cases. There was no significant difference in survival between molecular subtypes in RGC patients.CONCLUSIONRGC was associated with EBV positivity and higher rates of co-altered expression profiles compared to PGC. According to the molecular classification, there was no significant difference in survival between the subtypes of RGC.     

Effect of preoperative nutrition therapy type and duration on short-time outcomes in gastric cancer patient with gastric outlet obstruction

ObjectiveTo avoid perioperative complications caused malnutrition, nutrition therapy is necessary in gastric outlet obstruction (GOO) patients. Compared to parenteral nutrition (PN), enteral nutrition (EN) is associated with many advantages. This study aimed to investigate whether preoperative EN has beneficial clinical effects compared to preoperative PN in gastric cancer patients with GOO undergoing surgery.MethodsAccording to the methods of preoperative nutrition therapy, 143 patients were divided into EN group (n=42) and PN group (n=101) between January 2013 and December 2017 at the Chinese People’s Liberation Army General Hospital. Multiple logistic regression models were used to assess the association between the methods of preoperative nutrition therapy and postoperative day of flatus passage. The generalized additive model and two-piecewise linear regression model were used to calculate the inflection point of the preoperative nutritional therapy time on the postoperative day of flatus passage in the PN group.ResultsEN shortened the postoperative day of flatus passage in gastric cancer patients with GOO, which is a protective factor, especially in patients who underwent non-radical operations and the postoperative day of flatus passage reduced when the preoperative PN therapy was up to 3 d and a longer PN therapy (>3 d) did not accelerate the postoperative recovery of gastrointestinal functions.ConclusionsPreoperative EN therapy would benefit gastric cancer patients with GOO by accelerating postoperative recovery. For patients with absolute obstruction, no more than 3-day PN therapy is recommended if patients can tolerate general anesthesia and surgery.     

Survival prediction for terminally ill cancer patients: revision of the palliative prognostic score with incorporation of delirium

Purpose.

An existing and validated palliative prognostic (PaP) score predicts survival in terminally ill cancer patients based on dyspnea, anorexia, Karnofsky performance status score, clinical prediction of survival, total WBC, and lymphocyte percentage. The PaP score assigns patients to three different risk groups according to a 30-day survival probability—group A, >70%; group B, 30%–70%; group C, <30%. The impact of delirium is known but was not incorporated into the PaP score.

Materials and Methods.

Our aim was to incorporate information on delirium into the PaP score based on a retrospective series of 361 terminally ill cancer patients. We followed the approach of “validation by calibration,” proposed by van Houwelingen and later adapted by Miceli for achieving score revision with inclusion of a new variable. The discriminating performance of the scores was estimated using the K statistic.

Results.

The prognostic contribution of delirium was confirmed as statistically significant (p < .001) and the variable was accordingly incorporated into the PaP score (D-PaP score). Following this revision, 30-day survival estimates in groups A, B, and C were 83%, 50%, and 9% for the D-PaP score and 87%, 51%, and 16% for the PaP score, respectively. The overall performance of the D-PaP score was better than that of the PaP score.

Conclusion.

The revision of the PaP score was carried out by modifying the cutoff values used for prognostic grouping without, however, affecting the partial scores of the original tool. The performance of the D-PaP score was better than that of the PaP score and its key feature of simplicity was maintained.