Jose Luis Hernandez

Intraoperative and external radiotherapy in resected gastric cancer: Updated report of a phase II trial

From September 1984 to August 1991, 48 evaluable patients with resected gastric cancer and apparent disease confined to locoregional area were treated with intraoperative electron beam boost to the celiac axis and peripancreatic nodal areas (15 Gy) and external irradiation (40 to 46 Gy in 4 to 5 weeks) including the gastric bed and upper abdominal nodal draining regions. At the time of evaluation for IORT, the disease was primary in 38 cases, recurrent but resectable in four (anastomosis), and unresectable in four (nodal). Post operative complications were reversible. Acute tolerance to the complete treatment program was acceptable. Late complications included life-threatening events: Six episodes of gastro intestinal bleeding (three of them had an arteriographic documentation of arterioenteric fistula) and nine with severe enteritis (five required reoperation). Other long-term treatment related complications were six cases of vertebral collapse. The median follow-up time for the entire group is 22 months. Locoregional recurrence/persistence of disease has been identified in five patients (three with residual and/or recurrent postsurgical tumor). Systemic tumor progression has been detected in 15 patients (11 in intra-abdominal sites). Overall actuarial survival for patients with positive or negative serosal involvement was 33% versus 56%. It is concluded that the treatment program described is able to induce a high locoregional tumor control rate (100%) when used strictly in an adjuvant setting and might control long term, a small portion of patients not amenable for curative surgery (2 out of 8 patients with confirmed residual post-surgical disease). Gastrointestinal bleeding and enteritis are findings that indicate treatment intensity at the upper limits of tissue tolerance. Assessment of long term tolerance of pancreatic parenchyma and large blood vessels (tissues included in the IRORT field) are pending for longer follow-up and the appropriate selective studies.

Patterns of failure and long-term results in high-risk resected gastric cancer treated with postoperative radiotherapy with or without intraoperative electron boost

To evaluate the possible role of adjuvant radiotherapy in the management of high‐risk resected gastric carcinoma.

Intraoperative and external beam radiotherapy in advanced resectable gastric cancer: Technical description and preliminary results

Twenty-two patients with resectable gastric cancer treated with intraoperative radiotherapy and external beam irradiation, in a Phase I-II oriented study, were analyzed. Tumor Stages were III & IV in 18 cases (82%). Tumor histology was described as diffuse undifferentiated type in 14 cases (63%). Following surgical resection of the primary tumor, IORT 15 Gy was delivered in the celiac axis area, using high energy electron beams ranging from 9 to 20 MeV. External beam irradiation fields covered the draining nodal areas of the upper abdomen and the gastric bed. There were no postoperative deaths. Reversible postoperative complications were recorded in 14 patients (63%). Long term complications observed were vertebral collapse and liver hemangiomas. First sites of recurrence have been: hepatic hilum (three cases), peritoneum combined with central axis nodes (two cases), liver metastasis (one case), and lung metastasis (one case). Survival data shows a follow-up period ranging from 1+ to 33+ months, with a median survival time for the entire group of 13+ months. At the time of this report, 16 patients (72%) are still alive and six have died (four from progressive malignant disease and two from intercurrent disease). From this preliminary data, it can be concluded that a combined approach with surgical resection, intraoperative radiotherapy, and external beam irradiation is feasible in advanced gastric carcinoma, and is not limited by toxicity or any complications observed. Despite this intense loco-regional therapeutic approach, the upper abdominal failure rate has been demonstrated in 22% of the cases.

Four-Week Neoadjuvant Intensity-Modulated Radiation Therapy With Concurrent Capecitabine and Oxaliplatin in Locally Advanced Rectal Cancer Patients: A Validation Phase II Trial

PURPOSE To validate tolerance and pathological complete response rate (pCR) of a 4-week preoperative course of intensity-modulated radiation therapy (IMRT) with concurrent capecitabine and oxaliplatin (CAPOX) in patients with locally advanced rectal cancer. METHODS AND MATERIALS Patients with T3 to T4 and/or N+ rectal cancer received preoperative IMRT (47.5 Gy in 19 fractions) with concurrent capecitabine (825 mg/m(2) b.i.d., Monday to Friday) and oxaliplatin (60 mg/m(2) on Days 1, 8, and 15). Surgery was scheduled 4 to 6 weeks after the completion of chemoradiation. Primary end points were toxicity and pathological response rate. Local control (LC), disease-free survival (DFS), and overall survival (OS) were also analyzed. RESULTS A total of 100 patients were evaluated. Grade 1 to 2 proctitis was observed in 73 patients (73%). Grade 3 diarrhea occurred in 9% of the patients. Grade 3 proctitis in 18% of the first 50 patients led to reduction of the dose per fraction to 47.5 Gy in 20 treatments. The rate of Grade 3 proctitis decreased to 4% thereafter (odds ratio, 0.27). A total of 99 patients underwent surgery. A pCR was observed in 13% of the patients, major response (96-100% of histological response) in 48%, and pN downstaging in 78%. An R0 resection was performed in 97% of the patients. After a median follow-up of 55 months, the LC, DFS, and OS rates were 100%, 84%, and 87%, respectively. CONCLUSIONS Preoperative CAPOX-IMRT therapy (47.5 Gy in 20 fractions) is feasible and safe, and produces major pathological responses in approximately 50% of patients.

Análisis del Registro Nacional Español de la Cirugía Laparoscópica del Páncreas

Resumen Introduccion En el pasado, la experiencia de la cirugia laparoscopica del pancreas se mantenia limitada a experiencias individuales con un reducido nucleo de pacientes. El reciente estudio multicentrico europeo ha permitido conocer los limites y los resultados de la tecnica. En este trabajo se presenta el analisis de los resultados del Registro Nacional Espanol de la Cirugia Laparoscopica del Pancreas (RNEP). Material y metodos Se ha incluido a 132 pacientes con lesiones localizadas en el pancreas izquierdo: 42 tumores neuroendocrinos, 40 neoplasias quisticas, 24 quistes y seudoquistes, 8 tumores inflamatorios, 8 carcinomas ductales, 7 neoplasias papilares mucinosa, 1 carcinoma acinar, 2 tumores solidos seudopapilares. Resultados El indice de conversion fue del 9,7%. La tecnica de enucleacion se realizo tan solo en pacientes portadores de un insulinoma. La pancreatectomia distal con preservacion esplenica fue la utilizada con mas frecuencia. La mortalidad fue nula y, como morbilidad, la fistula pancreatica aparecio en el 16% de los casos. Conclusiones A pesar de que el numero de hospitales espanoles es limitado, los resultados obtenidos hacen esperar una mayor experiencia en un futuro proximo.

Role of histological regression grade after two neoadjuvant approaches with or without radiotherapy in locally advanced gastric cancer

Background:The degree of histopathological response after neoadjuvant therapy in locally advanced gastric cancer (GC) is a key determinant of patients’ long-term outcome. We aimed to assess the pattern of histopathological regression after two neoadjuvant approaches and its impact on survival times.Methods:Regression grade of the primary tumour (Becker criteria) and the degree of nodal response by a 4-point scale (grades A–D) were assessed. Grade A—true negative lymph nodes (LNs); grade B and C—infiltrated LNs with any or little evidence of nodal response; and grade D—complete pathological response in a previously infiltrated LN. A favourable pathological response was defined as Becker Ia–b and grade D.Results:From 2004 to 2014, 80 patients with GC (cT3–4/N+ by CT-scan/EUS) were treated with either preoperative chemotherapy (ChT, n=34) or chemoradiation (CRT, n=46). Patients in the CRT group had a higher likelihood of achieving a Becker Ia–b response (58 vs 32%, P=0.001), a grade D nodal regression (30 vs 6%, P=0.009) and a favourable pathological response (23 vs 3%; P=0.019). Patients with a grade D nodal response had a longer 5-year PFS and OS compared with those with a grade B or C response. Patients with a baseline negative LN status had similar outcomes irrespective of the preoperative therapy received (5-year OS; ChT vs CRT, 58 vs 51%, P=0.92).Conclusions:Preoperative chemoradiation increases the likelihood of achieving favourable histopathological features that correlate with a 5-year OS>70% in GC patients.

Influence of Hepatic Ischemia-Reperfusion Injury on Tacrolimus Acute Renal Toxicity in Pigs

H T E DEVELOPMENT of new immunosuppressants has been a determining factor in the recent surge in organ transplants. Tacrolimus, which was introduced in clinical practice by Starzl in 1989, has proved to be useful for prevention and treatment of rejection. Among its side effects, nephrotoxicity is of particular importance. The precipitating causes of acute nephrotoxicity (ANT), which may affect 35% to 45% of liver transplant patients are uncertain, but possibly include early graft malfunction, a phenomenon related to ischemia and reperfusion injuries, which result at least in part from shortcomings in the organ preservation. To shed light on the relationship between ischemic liver injury and ANT caused by tacrolimus, we designed a comparative experimental study of the kidney damage generated in two experimental models of hepatic ischemia-reperfusion injury: non–heart-beating donor and an ischemia–reperfusion model with the organ in situ.

Effect of treatment with tranexamic acid on complement activation and ischemia reperfusion in liver transplantation in pigs.

COMPLEMENT is gradually being considered in ischemia-reperfusion, especially in xenotransplantation. Reperfusion injury is characterized by deposition of C3 and C5b-9. Complement inhibitors are used in amelioration of warm ischemia and rejection episodes. Tranexamic acid (Amca), a synthetic antifibrinolytic agent, has proven to be effective in acquired angioedema (a deficiency of the C1 inhibitor [Ci-inh]). Because of the increased risk of severe fibrinolysis, Amca is often used during orthotopic liver transplantation (OLT). Although no report of the use of Amca was found in the treatment of ischemia-reperfusion injury, the anticomplement effect of Amca has been demonstrated. Our aim was to study the complement activation and the effect of Amca on complement and ischemia-reperfusion injury in a liver allograft with donor warm ischemia.

Metabolic and immunohistochemical asessment of endocrine pancreatic function after orthotopic multivisceral transplantation

IT is well known that pancreatic allografts normalize hyperglycemia a few hours after reperfusion. Endocrine function has been intensively studied in pancreas allografts from a biochemical point of view. Outstanding among functional studies is intravenous (IV) glucagon test, which has rarely been used in pancreas transplantation. However, there is little information on early histochemical aspects of pancreas transplantation and endocrine function has not been properly studied in multivisceral transplantation with the pancreas allograft draining into the portal vein of the liver graft. We studied the endocrine function of the orthotopically transplanted pancreas after multiorgan procurement in a multivisceral transplantation model in a previously reported model.

Pancreatic preservation in a multiorgan procurement procedure and transplantation.

U M LTIORGAN harvesting for individual organ transplantation is well defined according to the principles of Starzl. However, some pancreatic transplant surgeons believe the pancreas should not suffer hyperperfusion as occurs in multiorgan harvesting. This is in conflict with the need of all donor organs for transplantation and specially when multivisceral transplantation is planned. We believe that the pancreas is not so sensitive to high-volume flushing: most pancreata are harvested from multiorgan donors with good functional results. Even when flushing to the pan-creas in the adult donor is only 2 L, severe allograft pancreatitis has been reported in multivisceral transplantation. There must be some other etiologic factors of pancreatic preservation injury, namely warm ischemia and preservation time. We studied the quality of pancreas preservation in a multiorgan conventional preservation and orthotopic multivisceral transplantation technique.